Affinage

DMRT1

Doublesex- and mab-3-related transcription factor 1 · UniProt Q9Y5R6

Length
373 aa
Mass
39.5 kDa
Annotated
2026-06-09
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DMRT1 is a deeply conserved DM-domain transcription factor that acts as the master regulator of male gonadal fate across vertebrates, both initiating and maintaining testis identity while antagonizing the female regulatory program (PMID:11040213, PMID:21775990, PMID:25725066). It functions as a bifunctional regulator, occupying ~1,400 promoter-proximal sites genome-wide and activating male-promoting genes while repressing female- and pluripotency-associated genes in a cell-type-specific manner across Sertoli and germ cells (PMID:20616082). On the male-promoting side it directly activates Sox9b in tilapia (PMID:30415011), cooperates with Sf1 to induce gsdf (PMID:27027772), and behaves as a pioneer factor that opens chromatin and recruits SOX9 to newly accessible regions to consolidate Sertoli-cell fate (PMID:34096593). On the repressive side it silences the female determinant Foxl2 — sufficient, even in adult ovary, to reprogram granulosa cells into Sertoli-like cells — and in germ cells directly represses the pluripotency factors Sox2, Esrrb, and Nr5a2/Lrh1 to prevent teratoma formation (PMID:21775990, PMID:25683803, PMID:20007774, PMID:23473982). In the germ line DMRT1 governs the mitosis-to-meiosis switch by directly repressing Stra8 and restricting retinoic-acid responsiveness in testis while activating Stra8 to promote meiosis in the fetal ovary, and it sustains spermatogonial stem cells in part through Plzf (PMID:20951351, PMID:21621532, PMID:27583450). DMRT1 also enforces testicular immune homeostasis by transcriptionally activating Spry1, whose product binds NF-κB1 to block p65 nuclear translocation (PMID:37070575). Its own expression is driven in Sertoli cells by GATA4 and by Sp1/Sp3/Egr1 elements, modulated by FSH/cAMP-PKA signaling, and its DM-domain NLS mediates importin-β1-dependent nuclear import (PMID:14673170, PMID:11870074, PMID:11181532, PMID:17459496). Across birds, reptiles, fish and amphibians DMRT1 is necessary and sufficient for male development, with avian sex determination depending on DMRT1 dosage (PMID:19710650, PMID:33658372, PMID:28506988, PMID:24105480, PMID:28667307, PMID:20573695).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1999 Medium

    Establishing that Dmrt1 is a DM-domain gene with sex- and cell-type-specific gonadal expression placed it as a candidate sex-determination regulator before any functional data existed.

    Evidence In situ hybridization, RT-PCR and immunolocalization in mouse embryonic gonads

    PMID:10545231

    Open questions at the time
    • Expression alone did not establish function or direct targets
    • Did not distinguish Sertoli vs germ cell requirements
  2. 2000 High

    Loss-of-function established that Dmrt1 is required for postnatal male but not female gonad development, defining its core role.

    Evidence Germline knockout mouse with histological phenotyping

    PMID:11040213

    Open questions at the time
    • Did not separate cell-autonomous from non-autonomous roles
    • No molecular targets identified
    • Did not address initiation vs maintenance
  3. 2002 High

    Identifying the cis-elements and trans-factors driving Dmrt1 expression answered how the gene is itself transcriptionally controlled in Sertoli cells.

    Evidence DNase I footprinting, EMSA, mutagenesis and transfection in primary Sertoli cells (Sp1/Sp3/Egr1); GATA4 footprinting/EMSA with in vivo Fog2-null validation

    PMID:11870074 PMID:14673170

    Open questions at the time
    • How these inputs are integrated developmentally is unresolved
    • No structural basis for promoter assembly
  4. 2007 High

    Conditional targeting resolved that DMRT1 acts both cell-autonomously in Sertoli cells and germ cells and non-autonomously to support the germ line, and importin-β1 was shown to drive its nuclear import.

    Evidence Cell-type-specific Cre deletion in mouse; co-IP, in vitro transport reconstitution and antibody inhibition for importin-β1

    PMID:17459496 PMID:17540358

    Open questions at the time
    • The non-autonomous signal to germ cells was not identified
    • Regulation of nuclear import in vivo not defined
  5. 2010 High

    Genome-wide ChIP plus conditional KO defined DMRT1 as a bifunctional regulator with cell-type-specific targets, including direct control of the mitosis-to-meiosis switch via Stra8 repression and Sohlh1 activation.

    Evidence ChIP/ChIP-chip combined with conditional gene targeting and expression profiling in mouse testis

    PMID:20616082 PMID:20951351

    Open questions at the time
    • How activation vs repression decisions are made at individual sites is unclear
    • Cofactors directing bifunctionality not defined
  6. 2011 High

    Conditional adult deletion showed DMRT1 is required continuously to maintain testis fate by repressing Foxl2, while fetal-ovary work showed it can also activate Stra8 to promote oogenesis, revealing context-dependent target outcomes.

    Evidence Sertoli-specific deletion with hormone assays; ovarian ChIP-chip/qChIP and KO phenotyping in mouse

    PMID:21621532 PMID:21775990

    Open questions at the time
    • Molecular basis for opposite Stra8 regulation in testis vs ovary unresolved
    • Mediators of Sertoli-to-granulosa reprogramming not fully defined
  7. 2013 Medium

    ChIP-seq and germ-cell knockdown defined a DMRT1-Sox2 repression cascade controlling pluripotency and teratoma susceptibility in the germ line.

    Evidence ChIP-seq and conditional targeting in mouse testis; siRNA knockdown and rescue in germline stem cells

    PMID:23473982 PMID:24029916

    Open questions at the time
    • Single-lab epistasis for some interactions
    • Mechanism of indirect Gfra1/GDNF activation not direct
  8. 2015 High

    Gain-of-function established that DMRT1 is sufficient to trigger primary testis determination and to reprogram ovarian cells, elevating it from required factor to fate-determining switch.

    Evidence Wt1-BAC transgenic overexpression in XX fetal gonads; conditional Dmrt1 transgene in ovary with scRNA-seq

    PMID:25683803 PMID:25725066

    Open questions at the time
    • Identity of single-cell-defined mediators not functionally validated
    • Whether SOX9-independent silencing of Foxl2 is direct unresolved
  9. 2021 High

    Combined ATAC-seq/ChIP-seq with Sox9/Sox8 epistasis established DMRT1 as a pioneer factor that opens chromatin and licenses SOX9 binding, defining the mechanism of male fate reinforcement.

    Evidence Conditional transgene with ATAC-seq, ChIP-seq, conditional Sox9/Sox8 KO and 3D chromatin analysis

    PMID:34096593

    Open questions at the time
    • Biochemical basis of nucleosome engagement not resolved
    • Generality of pioneer activity at all target classes untested
  10. 2023 Medium

    A DMRT1–SPRY1–NF-κB axis was defined, extending DMRT1 function from cell-fate control to suppression of testicular inflammation and protection of the blood-testis barrier.

    Evidence ChIP-seq/RNA-seq for Spry1 activation, IP-MS and co-IP for SPRY1–NF-κB1 binding, in vivo knockdown

    PMID:33420764 PMID:37070575

    Open questions at the time
    • Single-lab interaction data
    • Direct vs indirect contribution to barrier integrity not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DMRT1 chooses between activation and repression at individual loci, and the full set of cofactors that direct its bifunctional and pioneer activities, remains undefined.
  • No structural model of DMRT1 on chromatin with cofactors
  • Determinants of cell-type-specific target selection unknown
  • Human Mendelian disease link not established in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1474165 Reproduction 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
GATA4IMPORTIN-BETA1SF1SOX9

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Murine Dmrt1 is essential for postnatal testis differentiation; Dmrt1 null mutant males show severely dysgenic testes while mutant females are fertile, establishing Dmrt1 as required for male but not female gonad development in mammals. Knockout mouse (loss-of-function), histological and phenotypic analysis Genes & development High 11040213
1999 Dmrt1 encodes a DM domain (zinc finger-like DNA-binding motif) protein and is expressed exclusively in the genital ridge of early XX and XY mouse embryos, becoming XY-specific as gonadogenesis proceeds; expressed in both Sertoli cells and germ cells of the testis. In situ hybridization, RT-PCR, immunolocalization Developmental biology Medium 10545231
2009 RNAi knockdown of DMRT1 in ZZ chicken embryos in ovo leads to feminization of gonads, with female-like histology, disorganized testis cords, loss of SOX9, and ectopic activation of aromatase, demonstrating DMRT1 is required for testis determination in birds. RNA interference (RNAi) knockdown in ovo, immunofluorescence, in situ hybridization Nature High 19710650
2011 Loss of DMRT1 in mouse Sertoli cells, even in adults, activates Foxl2 and reprograms Sertoli cells into granulosa cells, with theca cell formation, estrogen production, and feminization of germ cells; DMRT1 is required to maintain mammalian testis determination postnatally by antagonizing the female regulatory network involving FOXL2. Conditional gene targeting (Sertoli-cell-specific Dmrt1 deletion), immunohistochemistry, hormone assays, gene expression analysis Nature High 21775990
2010 DMRT1 determines whether male germ cells (spermatogonia) undergo mitosis/spermatogonial differentiation or enter meiosis: loss of Dmrt1 causes spermatogonia to precociously enter meiosis. Mechanistically, DMRT1 restricts retinoic acid (RA) responsiveness in spermatogonia, directly represses Stra8 transcription, and activates Sohlh1 transcription. Conditional gene targeting in mouse, mRNA expression profiling, chromatin immunoprecipitation (ChIP) Developmental cell High 20951351
2010 Genome-wide ChIP identified ~1,400 promoter-proximal regions bound by DMRT1 in the juvenile mouse testis. DMRT1 is a bifunctional transcriptional regulator—activating some genes and repressing others—with cell-type-specific (Sertoli vs. germ cell) differences in DNA binding and regulation. DMRT1 binds its own promoter and those of six other Dmrt genes, indicating auto- and cross-regulation. In vivo binding is enriched at a motif similar to the DMRT1 in vitro preference. ChIP combined with conditional gene targeting and mRNA expression analysis (ChIP + conditional KO + expression profiling) Proceedings of the National Academy of Sciences of the United States of America High 20616082
2009 DMRT1 is required in fetal germ cells (not Sertoli cells) to prevent teratoma formation in 129Sv mice; loss of Dmrt1 causes failure to arrest mitosis and ectopic expression of pluripotency markers. DMRT1 directly represses the pluripotency regulator Sox2 and indirectly activates the GDNF coreceptor Ret, as shown by ChIP and expression analysis. Conditional gene targeting (germ-cell-specific deletion), chromatin immunoprecipitation (ChIP), mRNA expression profiling Proceedings of the National Academy of Sciences of the United States of America High 20007774
2011 DMRT1 promotes oogenesis in the fetal ovary by transcriptional activation of Stra8 in fetal germ cells; Dmrt1 mutant females show greatly reduced STRA8 expression, defective meiotic prophase, and fewer primordial follicles. ChIP-chip and qChIP indicate this activation is likely direct, showing sex-specific control of Stra8 (activation in ovary, repression in testis). Dmrt1 knockout mouse, genome-wide ChIP-chip, quantitative ChIP (qChIP), mRNA expression profiling, immunofluorescence Developmental biology High 21621532
2007 Conditional gene targeting shows Dmrt1 is required cell-autonomously in Sertoli cells for postnatal differentiation and non-autonomously to maintain the germ line; Dmrt1 is required cell-autonomously in germ cells for radial migration, mitotic reactivation, and survival. Both cell-autonomous and non-autonomous functions are thus established. Conditional gene targeting (cell-type-specific Cre-mediated deletion in Sertoli cells vs. germ cells), histology, immunohistochemistry Developmental biology High 17540358
2015 Conditional expression of a Dmrt1 transgene in the mouse ovary is sufficient to silence Foxl2 and reprogram juvenile and adult granulosa cells into Sertoli-like cells, triggering formation of structures resembling male seminiferous tubules; DMRT1 can silence Foxl2 even in the absence of Sox8 and Sox9. Single-cell RNA sequencing identified dynamically expressed candidate mediators of this reprogramming. Conditional transgene expression in vivo, single-cell RNA sequencing, mRNA profiling, immunohistochemistry Current biology : CB High 25683803
2021 DMRT1 recruits SOX9 during sexual cell fate reprogramming: DMRT1 opens chromatin (pioneer factor activity) at many differentially accessible regions and is required for SOX9 binding at most of these sites. DMRT1 only partially reprograms the ovarian transcriptome in the absence of SOX9/SOX8, demonstrating functional cooperation between DMRT1 and SOX9. Conditional transgene, ATAC-seq, ChIP-seq, conditional Sox9/Sox8 knockout, RNA-seq, 3D chromatin contact analysis Nucleic acids research High 34096593
2015 Transgenic overexpression of Dmrt1 in XX mouse fetal gonads using a Wt1-BAC system drives testicular differentiation and male secondary sex development: repression of Wnt4 and Foxl2, activation of Sox9 and Sertoli cell formation, steroidogenic Leydig cell development, and male reproductive tract formation. This demonstrates Dmrt1 is sufficient to trigger primary testis determination in mammals. Transgenic overexpression in vivo (Wt1-BAC transgene), immunohistochemistry, gene expression analysis Development (Cambridge, England) High 25725066
2016 DMRT1 is required for spermatogonial stem cell (SSC) maintenance and regulates expression of Plzf (another transcription factor required for SSC maintenance). Dmrt1 is also required in Ngn3-positive progenitor cells for recovery of spermatogenesis after germ cell depletion, enabling progenitor cells to replenish the Id4-GFP+ SSC pool. Conditional gene targeting (Dmrt1 deletion in Ngn3+ cells), busulfan depletion assay, Id4-GFP reporter, immunohistochemistry PLoS genetics High 27583450
2004 GATA4 directly regulates testis expression of Dmrt1: GATA4 binds a region between -3.2 and -2.8 kb of the Dmrt1 promoter, as shown by DNase I footprinting and EMSA; GATA4-response elements are required for full Sertoli-cell-specific expression, validated by Dmrt1 expression analysis in Fog2 null gonads in vivo. Transient transfection, DNase I footprinting, EMSA, promoter deletion analysis, in vivo Fog2 mutant analysis Molecular and cellular biology High 14673170
2002 Sp1, Sp3, and Egr1 bind activating elements in the Dmrt1 proximal promoter (downstream of -150 bp) in Sertoli cells; two additional elements repress the promoter. Site-directed mutagenesis confirmed these elements regulate Dmrt1 expression. DNase I footprinting, EMSA, site-directed mutagenesis, transient transfection in primary Sertoli cells Biology of reproduction High 11870074
2007 DMRT1 nuclear import is mediated by importin-beta1: a functional NLS within the DM domain (residues K92 and R93 are critical) was identified; importin-beta1 binds directly to DMRT1 via the DM domain; co-IP confirmed the interaction in Sertoli cells in vivo; blocking importin-beta1 with antibody inhibits DMRT1 nuclear import. Site-directed mutagenesis, co-immunoprecipitation, in vitro nuclear transport assay in digitonin-permeabilized cells, antibody microinjection Biochimica et biophysica acta High 17459496
2001 Dmrt1 mRNA levels in postnatal rat Sertoli cells are upregulated by FSH and 8-bromo-cAMP in a transcription-dependent, translation-independent manner requiring protein kinase A activation; phorbol esters (PMA) inhibit expression, indicating PKC-dependent repression. cAMP response was blocked by actinomycin D but not cycloheximide. RNase protection assay, primary Sertoli cell culture, pharmacological inhibitors (H89, actinomycin D, cycloheximide, PMA, FSH treatment) Endocrinology Medium 11181532
2013 DMRT1 directly represses Esrrb, Nr5a2/Lrh1, and Sox2 as shown by ChIP-seq in fetal mouse testis, controlling germ cell pluripotency. Conditional deletion of Gfra1 (but not Ret) in fetal germ cells on a 129Sv background modestly elevated teratoma incidence, consistent with DMRT1 indirectly activating Gfra1/GDNF signaling. A strong genetic interaction between Dmrt1 and Nanos3 was uncovered by conditional targeting. ChIP-seq, conditional gene targeting (Nanos3-cre), mRNA expression profiling, teratoma susceptibility assay Developmental biology Medium 23473982
2013 Dmrt1 depletion in germline stem (GS) cells up-regulates Sox2, which then up-regulates Oct4 to produce pluripotent cells. Functional screening identified Dmrt1 as directly maintaining SSC identity by repressing Sox2 in a Dmrt1-Sox2 cascade, critical for regulating pluripotency in spermatogonial stem cells. siRNA knockdown in GS cells, lentiviral Sox2 transduction, pluripotency assays, functional screening Genes & development Medium 24029916
2021 In human PGC-like cells in vitro, induction of DMRT1 together with SOX17 promotes epigenetic resetting with global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites, and activates DAZL expression, establishing a germline commitment program. hESC-derived PGC-like cell differentiation, epigenome profiling (5hmC/5mC), ChIP, gene expression analysis Nature cell biology Medium 37709822
2010 In Xenopus laevis, DM-W (a W-chromosome paralog of DMRT1) shares a DNA-binding sequence with DMRT1 but lacks the transactivation domain; DM-W dose-dependently antagonizes DMRT1 transcriptional activity on a DMRT1-driven luciferase reporter in 293 cells. In vivo, ectopic DMRT1 in ZW individuals induces testicular development, while DM-W knockdown causes testicular-like gonads. DMRT1 and DM-W thus have opposing functions in sex determination. Luciferase reporter assay, transgenic DM-W knockdown in Xenopus, ectopic DMRT1 expression in ZW tadpoles Development (Cambridge, England) High 20573695
2021 CRISPR-Cas9-based monoallelic targeting of DMRT1 in ZZ chicken embryos produces birds that develop ovaries instead of testes, demonstrating that avian sex determination depends on DMRT1 dosage (two functional copies required for testis development). These ZZ birds with ovaries showed female molecular markers and follicular development but retained male external appearance (cell-autonomous sex identity). Blocking estrogen synthesis in ZW embryos lacking DMRT1 resulted in ovarian fate, indicating DMRT1 and estrogen both contribute to avian primary sex determination. CRISPR-Cas9 monoallelic targeting, sterile surrogate hosts, immunohistochemistry, histology, hormone assays Proceedings of the National Academy of Sciences of the United States of America High 33658372
2017 Loss-of-function (CRISPR/Cas9) and gain-of-function (ectopic expression) analyses in the red-eared slider turtle T. scripta demonstrate Dmrt1 is both necessary and sufficient to initiate male development; Dmrt1 has temperature-dependent, sexually dimorphic expression preceding gonadal sex differentiation, and DNA methylation of the Dmrt1 promoter correlates with temperature. CRISPR/Cas9 loss-of-function, ectopic expression (gain-of-function), DNA methylation assay, quantitative expression analysis Development (Cambridge, England) High 28506988
2014 Overexpression of DMRT1 in female chicken embryonic gonads induces male pathway genes (SOX9, AMH, HEMGN), antagonizes the female pathway (reduces aromatase expression), and causes cord-like structures with retarded cortical development, demonstrating DMRT1 is sufficient to induce testicular differentiation in birds. In ovo overexpression, in situ hybridization, RT-PCR, immunohistochemistry Developmental biology High 24576538
2013 In Nile tilapia, TALEN-mediated disruption of Dmrt1 in XY fish causes testicular regression, degenerated spermatogonia, proliferation of steroidogenic cells, and increased foxl2 and cyp19a1a expression with elevated estradiol; disruption of Foxl2 in XX fish caused oocyte degeneration, decreased aromatase, and complete sex reversal with high Dmrt1 and Cyp11b2. Dmrt1 and Foxl2 thus play antagonistic roles in sex differentiation via regulation of cyp19a1a and estrogen production. TALEN-mediated genome editing, histology, immunohistochemistry, RT-PCR, hormone assays Endocrinology High 24105480
2016 In Nile tilapia, Dmrt1 directly activates gsdf expression in a dose-dependent manner in the presence of Sf1 (but not alone), as shown by in vitro promoter analysis; gsdf is positioned genetically downstream of dmrt1 in the male sex determination pathway. Loss of gsdf leads to activation then loss of Dmrt1 expression and eventual sex reversal to female. CRISPR/Cas9 knockout of gsdf, luciferase promoter analysis, gene expression profiling, aromatase inhibitor rescue Molecular reproduction and development Medium 27027772
2018 In Nile tilapia, Dmrt1 directly binds a specific cis-regulatory element (CRE) near the translation start site of the Sox9b promoter and positively regulates Sox9b transcription, as demonstrated by luciferase reporter assay, site-directed mutagenesis, ChIP, and EMSA. Luciferase reporter assay, site-directed mutagenesis, ChIP, EMSA Gene High 30415011
2023 Dmrt1 transcriptionally activates Spry1 expression (shown by ChIP-seq and RNA-seq); SPRY1 protein then binds NF-κB1 (shown by IP-MS and co-IP) to prevent nuclear translocation of p65, thereby inhibiting NF-κB signaling and protecting the blood-testis barrier and immune homeostasis. Knockdown of Dmrt1 in mice causes widespread inflammatory response and spermatogenic cell loss. ChIP-seq, RNA-seq, immunoprecipitation-mass spectrometry (IP-MS), co-immunoprecipitation (Co-IP), siRNA knockdown in vivo Zoological research Medium 37070575
2021 In goat male germline stem cells, Dmrt1 recruits Plzf/Zbtb16 to repress the TLR4-dependent inflammatory signaling pathway and NF-κB, maintaining testicular immune homeostasis. SPRY1 binds NF-κB1 to prevent p65 nuclear translocation downstream of this axis. Dmrt1 knockdown, co-immunoprecipitation, gene expression analysis, immunohistochemistry Zoological research Medium 33420764
2016 miR-224 promotes differentiation of mouse spermatogonial stem cells (SSCs) by directly targeting DMRT1 (3'UTR); miR-224 overexpression increases GFRα1 and PLZF expression with concurrent down-regulation of DMRT1, and this is mediated through WNT/β-catenin signaling. miRNA mimics and inhibitors, luciferase 3'UTR reporter assay, Western blot, immunohistochemistry Journal of cellular and molecular medicine Medium 27099200
2010 In medaka, the autosomal dmrt1a gene regulates transcription of its duplicated Y-linked paralog dmrt1bY by binding to a Dmrt1 binding site nested within the dmrt1bY proximal promoter, a regulatory element derived from a transposable element inserted after gene duplication. This demonstrates DMRT1 autoregulation and cross-regulation of a paralog via a TE-derived regulatory element. Promoter luciferase assays, ChIP, transposable element sequence analysis, transgenic approaches PLoS genetics Medium 20169179
2006 The C-terminal region of Xenopus DMRT1 functions as a transactivation domain in cultured cells, as shown by a luciferase reporter assay using GAL4-DMRT1 fusion proteins. Luciferase reporter assay with GAL4 fusion proteins in cultured cells Development, growth & differentiation Medium 17118014
2021 DMRT1 drives reprogramming and propagation of germ cell tumor cells in vivo following OSKM-induced somatic reprogramming; DMRT1 expression is induced in PGC-related cells during reprogramming and the DMRT1-related epigenetic landscape is associated with trophoblast competence of reprogrammed cells. In vivo OSKM induction, DMRT1 gain-of-function, chromatin/epigenome analysis, iPSC derivation from tumor cells Nature communications Medium 34413299
2013 In zebrafish dmrt1/foxl3 tilapia double mutants, germline sexual fate is determined by the antagonistic interaction of dmrt1 and foxl3: loss of dmrt1 rescued germ cell sex reversal in foxl3 XX fish; sexual plasticity of germ cells requires the presence of both dmrt1 and foxl3. CRISPR/Cas9 double knockout, histology, gene expression analysis, hormone treatment Development (Cambridge, England) Medium 33741713
2017 In P. sinensis turtle, Dmrt1 knockdown (RNAi) in ZZ embryos causes male-to-female sex reversal with feminized gonads, decreased Amh and Sox9, and increased Cyp19a1 and Foxl2; ectopic Dmrt1 expression masculinizes ZW females and activates Amh and Sox9 while suppressing Cyp19a1 and Foxl2. Dmrt1 is both necessary and sufficient for male pathway initiation. RNA interference in ovo, ectopic expression, RT-PCR, immunohistochemistry Scientific reports High 28667307

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 The avian Z-linked gene DMRT1 is required for male sex determination in the chicken. Nature 577 19710650
2000 Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes & development 532 11040213
2011 DMRT1 prevents female reprogramming in the postnatal mammalian testis. Nature 463 21775990
1999 Expression of Dmrt1 in the genital ridge of mouse and chicken embryos suggests a role in vertebrate sexual development. Developmental biology 369 10545231
2010 Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nature genetics 278 20543847
2010 The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper that controls the mitosis versus meiosis decision in male germ cells. Developmental cell 274 20951351
2004 Two DM domain genes, DMY and DMRT1, involved in testicular differentiation and development in the medaka, Oryzias latipes. Developmental dynamics : an official publication of the American Association of Anatomists 235 15376325
2016 Dmrt1 is necessary for male sexual development in zebrafish. Developmental biology 204 27940159
2000 DMRT1 expression during gonadal differentiation and spermatogenesis in the rainbow trout, Oncorhynchus mykiss. Biochimica et biophysica acta 195 10978520
2006 Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene. Cancer research 172 16397242
2000 Temperature-dependent expression of turtle Dmrt1 prior to sexual differentiation. Genesis (New York, N.Y. : 2000) 172 10705377
2009 The DM domain protein DMRT1 is a dose-sensitive regulator of fetal germ cell proliferation and pluripotency. Proceedings of the National Academy of Sciences of the United States of America 156 20007774
2013 Antagonistic roles of Dmrt1 and Foxl2 in sex differentiation via estrogen production in tilapia as demonstrated by TALENs. Endocrinology 144 24105480
2005 Gene structure, multiple alternative splicing, and expression in gonads of zebrafish Dmrt1. Biochemical and biophysical research communications 143 15809088
2000 Conserved synteny between the chicken Z sex chromosome and human chromosome 9 includes the male regulatory gene DMRT1: a comparative (re)view on avian sex determination. Cytogenetics and cell genetics 139 10894941
2003 DMRT1 is upregulated in the gonads during female-to-male sex reversal in ZW chicken embryos. Biology of reproduction 134 12533420
2017 Distinct and Cooperative Roles of amh and dmrt1 in Self-Renewal and Differentiation of Male Germ Cells in Zebrafish. Genetics 133 28893856
2011 Dmrt1 genes at the crossroads: a widespread and central class of sexual development factors in fish. The FEBS journal 127 21281449
2007 Cell type-autonomous and non-autonomous requirements for Dmrt1 in postnatal testis differentiation. Developmental biology 123 17540358
2017 Genome editing reveals dmrt1 as an essential male sex-determining gene in Chinese tongue sole (Cynoglossus semilaevis). Scientific reports 121 28205594
2021 Primary sex determination in birds depends on DMRT1 dosage, but gonadal sex does not determine adult secondary sex characteristics. Proceedings of the National Academy of Sciences of the United States of America 118 33658372
2001 Genomic organization and expression of the doublesex-related gene cluster in vertebrates and detection of putative regulatory regions for DMRT1. Genomics 112 11543627
2012 Dmrt1 mutation causes a male-to-female sex reversal after the sex determination by Dmy in the medaka. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 111 22187367
2008 Sexual dimorphic expression of DMRT1 and Sox9a during gonadal differentiation and hormone-induced sex reversal in the teleost fish Nile tilapia (Oreochromis niloticus). Developmental dynamics : an official publication of the American Association of Anatomists 108 18095345
2007 Expression of Sox9, Mis, and Dmrt1 in the gonad of a species with temperature-dependent sex determination. Developmental dynamics : an official publication of the American Association of Anatomists 108 17326219
2002 Different patterns of anti-Müllerian hormone expression, as related to DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9 expression, in the chick differentiating gonads. Developmental dynamics : an official publication of the American Association of Anatomists 107 12412004
2013 Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1. PLoS genetics 105 23555275
2011 A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility. Human molecular genetics 105 21551455
2011 DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary. Developmental biology 105 21621532
2014 Over-expression of DMRT1 induces the male pathway in embryonic chicken gonads. Developmental biology 103 24576538
2010 Opposite roles of DMRT1 and its W-linked paralogue, DM-W, in sexual dimorphism of Xenopus laevis: implications of a ZZ/ZW-type sex-determining system. Development (Cambridge, England) 103 20573695
2006 Differential and spermatogenic cell-specific expression of DMRT1 during sex reversal in protogynous hermaphroditic groupers. Molecular and cellular endocrinology 102 17092636
2017 Dmrt1 induces the male pathway in a turtle species with temperature-dependent sex determination. Development (Cambridge, England) 101 28506988
2015 Sexual cell-fate reprogramming in the ovary by DMRT1. Current biology : CB 101 25683803
2002 The Dmrt1 expression in sex-reversed gonads of amphibians. General and comparative endocrinology 99 12225764
2016 DMRT1 Is Required for Mouse Spermatogonial Stem Cell Maintenance and Replenishment. PLoS genetics 97 27583450
2016 gsdf is a downstream gene of dmrt1 that functions in the male sex determination pathway of the Nile tilapia. Molecular reproduction and development 96 27027772
2007 Sex-specific differences in mouse DMRT1 expression are both cell type- and stage-dependent during gonad development. Biology of reproduction 88 17567962
2010 Transcriptional rewiring of the sex determining dmrt1 gene duplicate by transposable elements. PLoS genetics 87 20169179
2010 Evolution of the closely related, sex-related genes DM-W and DMRT1 in African clawed frogs (Xenopus). Evolution; international journal of organic evolution 85 21044062
2000 Sex-specific expression of an evolutionarily conserved male regulatory gene, DMRT1, in birds. Cytogenetics and cell genetics 84 10965136
2015 Female-to-male sex reversal in mice caused by transgenic overexpression of Dmrt1. Development (Cambridge, England) 83 25725066
2010 Genome-wide analysis of DNA binding and transcriptional regulation by the mammalian Doublesex homolog DMRT1 in the juvenile testis. Proceedings of the National Academy of Sciences of the United States of America 83 20616082
2008 Molecular cloning and quantitative expression of sexually dimorphic markers Dmrt1 and Foxl2 during female-to-male sex change in Epinephelus merra. General and comparative endocrinology 78 18452918
2017 Sex determination and maintenance: the role of DMRT1 and FOXL2. Asian journal of andrology 76 28091399
2007 The evolution of sex chromosomes and sex determination in vertebrates and the key role of DMRT1. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 75 18391511
2007 Estrogen-induced alterations in amh and dmrt1 expression signal for disruption in male sexual development in the zebrafish. Environmental science & technology 72 17937319
2002 DMRT1 in a ratite bird: evidence for a role in sex determination and discovery of a putative regulatory element. Cytogenetic and genome research 70 12900571
2005 Multiple alternative splicing and differential expression of dmrt1 during gonad transformation of the rice field eel. Biology of reproduction 68 16014815
2012 Testicular dmrt1 is involved in the sexual fate of the ovotestis in the protandrous black porgy. Biology of reproduction 65 22034528
2011 Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour. Journal of medical genetics 64 21617256
2013 CpG methylation of dmrt1 and cyp19a promoters in relation to their sexual dimorphic expression in the Japanese flounder Paralichthys olivaceus. Journal of fish biology 62 24372528
2009 Dimorphic expression of dmrt1 and cyp19a1 (ovarian aromatase) during early gonadal development in pejerrey, Odontesthes bonariensis. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 62 19276634
2017 Dmrt1 is required for primary male sexual differentiation in Chinese soft-shelled turtle Pelodiscus sinensis. Scientific reports 60 28667307
2020 Disruption of dmrt1 rescues the all-male phenotype of the cyp19a1a mutant in zebrafish - a novel insight into the roles of aromatase/estrogens in gonadal differentiation and early folliculogenesis. Development (Cambridge, England) 59 32001440
2013 Regulation of pluripotency in male germline stem cells by Dmrt1. Genes & development 55 24029916
2021 DMRT1: An Ancient Sexual Regulator Required for Human Gonadogenesis. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 54 34515237
2021 Germline sexual fate is determined by the antagonistic action of dmrt1 and foxl3/foxl2 in tilapia. Development (Cambridge, England) 52 33741713
2014 Evolutionary history of two divergent Dmrt1 genes reveals two rounds of polyploidy origins in gibel carp. Molecular phylogenetics and evolution 51 24859683
2015 Molecular cloning and expression analysis of dmrt1 and sox9 during gonad development and male reproductive cycle in the lambari fish, Astyanax altiparanae. Reproductive biology and endocrinology : RB&E 49 25577427
2004 Gata4 regulates testis expression of Dmrt1. Molecular and cellular biology 49 14673170
2010 A novel ncRNA gene from mouse chromosome 5 trans-splices with Dmrt1 on chromosome 19. Biochemical and biophysical research communications 47 20816665
2003 Expression of Dmrt1 protein in developing and in sex-reversed gonads of amphibians. Cytogenetic and genome research 46 14684998
2022 Transposon-induced epigenetic silencing in the X chromosome as a novel form of dmrt1 expression regulation during sex determination in the fighting fish. BMC biology 44 34996452
2021 The conserved sex regulator DMRT1 recruits SOX9 in sexual cell fate reprogramming. Nucleic acids research 44 34096593
2011 Associations between variants in KITLG, SPRY4, BAK1, and DMRT1 and pediatric germ cell tumors. Genes, chromosomes & cancer 44 22072546
2002 Sp1 and Egr1 regulate transcription of the Dmrt1 gene in Sertoli cells. Biology of reproduction 44 11870074
2017 Sex Reversal and Comparative Data Undermine the W Chromosome and Support Z-linked DMRT1 as the Regulator of Gonadal Sex Differentiation in Birds. Endocrinology 43 28911174
2007 mRNA expression analysis and the molecular basis of neonatal testis defects in Dmrt1 mutant mice. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 43 18391515
2003 Expression of Dmrt1 in a turtle with temperature-dependent sex determination. Cytogenetic and genome research 42 14684999
2013 Interaction between DMRT1 function and genetic background modulates signaling and pluripotency to control tumor susceptibility in the fetal germ line. Developmental biology 41 23473982
2018 Sex-specific dmrt1 and cyp19a1 methylation and alternative splicing in gonads of the protandrous hermaphrodite barramundi. PloS one 40 30226860
2023 Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility. Zoological research 38 37070575
2016 MicroRNA-224 regulates self-renewal of mouse spermatogonial stem cells via targeting DMRT1. Journal of cellular and molecular medicine 38 27099200
2001 Dmrt1 expression is regulated by follicle-stimulating hormone and phorbol esters in postnatal Sertoli cells. Endocrinology 38 11181532
2018 Dmrt1 directly regulates the transcription of the testis-biased Sox9b gene in Nile tilapia (Oreochromis niloticus). Gene 36 30415011
2006 Multiple alternative splicing in gonads of chicken DMRT1. Development genes and evolution 36 17120025
2003 Expression of DMRT1 in the mammalian ovary and testis--from marsupials to mice. Cytogenetic and genome research 36 14684988
2003 Cloning of the dmrt1 gene of Xiphophorus maculatus: dmY/dmrt1Y is not the master sex-determining gene in the platyfish. Gene 34 14604792
2013 A Wt1-Dmrt1 transgene restores DMRT1 to sertoli cells of Dmrt1(-/-) testes: a novel model of DMRT1-deficient germ cells. Biology of reproduction 33 23255335
2023 DMRT1 regulates human germline commitment. Nature cell biology 32 37709822
2006 Dmrt1 expression in response to estrogen treatment in a reptile with temperature-dependent sex determination. Journal of experimental zoology. Part B, Molecular and developmental evolution 32 16217798
2009 Gonadal sex differentiation and expression of Sox9a2, Dmrt1, and Foxl2 in Oryzias luzonensis. Genesis (New York, N.Y. : 2000) 30 19298014
2005 Molecular cloning of Dmrt1 and its expression in the gonad of Xenopus. Zoological science 30 15988164
2021 DMRT1-mediated reprogramming drives development of cancer resembling human germ cell tumors with features of totipotency. Nature communications 29 34413299
2010 Sexually dimorphic expression of dmrt1 in immature and mature Atlantic cod (Gadus morhua L.). Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 29 20363354
2021 Dmrt1 regulates the immune response by repressing the TLR4 signaling pathway in goat male germline stem cells. Zoological research 28 33420764
2017 Molecular Evolution of Two Distinct dmrt1 Promoters for Germ and Somatic Cells in Vertebrate Gonads. Molecular biology and evolution 28 27927791
2017 Dmrt1 polymorphism and sex-chromosome differentiation in Rana temporaria. Molecular ecology 28 28675502
2014 DMRT1 mutations are rarely associated with male infertility. Fertility and sterility 28 24934491
2021 DMRT1 gene disruption alone induces incomplete gonad feminization in chicken. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 34449112
2010 Frequent silence of chromosome 9p, homozygous DOCK8, DMRT1 and DMRT3 deletion at 9p24.3 in squamous cell carcinoma of the lung. International journal of oncology 27 20596660
2014 Expression characterization of testicular DMRT1 in both Sertoli cells and spermatogenic cells of polyploid gibel carp. Gene 26 25020260
2016 Trans-species variation in Dmrt1 is associated with sex determination in four European tree-frog species. Evolution; international journal of organic evolution 25 26920488
2007 Nuclear import of human sexual regulator DMRT1 is mediated by importin-beta. Biochimica et biophysica acta 25 17459496
2006 Expression and promoter analysis of Xenopus DMRT1 and functional characterization of the transactivation property of its protein. Development, growth & differentiation 25 17118014
2020 Alternative splicing and thermosensitive expression of Dmrt1 during urogenital development in the painted turtle, Chrysemys picta. PeerJ 24 32219017
2013 Sexual dimorphism of AMH, DMRT1 and RSPO1 localization in the developing gonads of six anuran species. The International journal of developmental biology 24 24623081
2012 Expression of dmrt1 and sox9 during gonadal development in the Siberian sturgeon (Acipenser baerii). Fish physiology and biochemistry 24 22688449
2012 Sexually dimorphic and ontogenetic expression of dmrt1, cyp19a1a and cyp19a1b in Gobiocypris rarus. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 23 22504107

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