Affinage

MSL2

E3 ubiquitin-protein ligase MSL2 · UniProt Q9HCI7

Length
577 aa
Mass
62.5 kDa
Annotated
2026-06-10
45 papers in source corpus 33 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MSL2 is the male-specific, limiting organizer of the Drosophila dosage compensation complex (DCC), the assembly that doubles transcription of the single male X chromosome (PMID:7781064, PMID:16179989). It is a RING-finger protein whose N-terminal RING domain nucleates complex assembly by binding MSL1, with the first zinc-binding site essential for the MSL2-MSL1 interaction and male viability (PMID:7781064, PMID:9736618); assembly of all MSL components on the X is mutually interdependent from early embryogenesis (PMID:8562424). MSL2 directs the complex to the X through a CXC domain that binds the MSL recognition element (MRE) DNA motif with low-nanomolar affinity, reading dinucleotides from the minor groove via a single arginine as resolved by crystallography (PMID:20139418, PMID:25452275), while a Zn3Cys9 cluster scaffolds the domain (PMID:23029009). X targeting is reinforced by direct interaction of the MSL2 disordered region with the zinc-finger of CLAMP, which is functionally redundant with CXC-mediated DNA binding for DCC recruitment (PMID:31320325, PMID:37602401), and by the low-complexity C-terminal domain, which integrates roX non-coding RNAs into a condensed compartment that restricts the complex to hundreds of X sites and is sufficient to nucleate ectopic dosage compensation in mammalian cells (PMID:18086881, PMID:33208948). Beyond complex scaffolding, MSL2 is a catalytic E3 ubiquitin ligase: with MSL1 it ubiquitylates histone H2B at K34 to drive trans-tail H3 K4/K79 methylation and transcription activation (PMID:21726816), and it autoubiquitylates and ubiquitylates excess MSL subunits for proteasomal degradation as a stoichiometry-control mechanism (PMID:23084834, PMID:38831503). In females, MSL2 protein is silenced post-transcriptionally: Sex-lethal (SXL) blocks msl-2 splicing and, acting cooperatively through 5' and 3' UTRs, recruits the co-repressors UNR, Hrp48, and HOW to inhibit 40S ribosome recruitment in a PABP- and eIF3d-dependent manner (PMID:9182767, PMID:16452508, PMID:19941818, PMID:29635389). In mammals MSL2 additionally functions in the DNA damage response, supporting non-homologous end joining and ubiquitylating 53BP1 (PMID:23874665), and a nervous-system conditional knockout in mice causes neurodevelopmental and cognitive deficits linked to reduced H4K16ac and loss of chromatin accessibility at disease genes (PMID:42168661).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1995 High

    Established that MSL2 is a RING-finger protein and the limiting organizing subunit of the dosage compensation complex, answering what controls male-specific assembly of MSL regulators on the X.

    Evidence Co-IP and immunofluorescence colocalization on polytene chromosomes, plus transgenic ectopic expression in females

    PMID:7588059 PMID:7781064 PMID:8562424

    Open questions at the time
    • Molecular basis of the RING domain interaction not yet mapped
    • DNA-binding activity inferred from sequence, not demonstrated
    • Mechanism of X-specific targeting unknown
  2. 1998 High

    Defined the RING finger as the MSL1-interaction module that nucleates complex assembly, mapping the assembly hierarchy to specific zinc-binding residues.

    Evidence Yeast two-hybrid, co-IP, RING finger mutagenesis correlated with in vivo male viability

    PMID:9736618

    Open questions at the time
    • Catalytic (E3 ligase) function of the RING not yet recognized
    • How the complex selects X sequences unresolved
  3. 2003 High

    Resolved how female translational silencing works, showing SXL blocks both splicing and translation of msl-2 and that initiation is inhibited at the 40S recruitment step via cooperative 5'/3' UTR sites.

    Evidence In vitro splicing, cell-free translation, ribosome association assays with UTR mutagenesis

    PMID:10545124 PMID:10617208 PMID:11565743 PMID:12769862 PMID:14532129 PMID:9182767

    Open questions at the time
    • Identity of recruited co-repressor proteins not yet known
    • Link between UTR co-repressor complex and ribosome blockade not mechanistically closed
  4. 2009 High

    Identified the SXL co-repressor machinery (UNR/PABP) and the biochemical step it targets, explaining how the 3' UTR complex represses initiation.

    Evidence mRNP purification with MS identification of UNR, RNAi, UNR-PABP interaction and ribosome-recruitment assays

    PMID:16452508 PMID:19941818

    Open questions at the time
    • Full co-repressor inventory incomplete at this stage
    • Kinetics of repressor assembly unresolved
  5. 2014 High

    Determined the structural and biochemical basis of X-chromosome DNA targeting, showing the CXC domain reads the MRE motif from the minor groove.

    Evidence Crystal structure of CXC-DNA, in vitro binding, mutagenesis with in vivo X localization; NMR of the Zn3Cys9 cluster

    PMID:20139418 PMID:23029009 PMID:25452275

    Open questions at the time
    • DNA binding alone insufficient to explain full X specificity
    • How roX RNA refines targeting not yet integrated
  6. 2020 High

    Showed that roX RNA and the MSL2 low-complexity C-terminal domain form a condensate that restricts the complex to the X and is portable to mammalian cells, explaining how chromosome-wide specificity is achieved.

    Evidence Domain swaps in Drosophila and mammalian cells, live condensate imaging, in vivo roX-CTD genetics

    PMID:16179989 PMID:18086881 PMID:33208948

    Open questions at the time
    • Physical basis of phase separation not fully defined
    • How condensation couples to transcriptional upregulation unresolved
  7. 2012 High

    Revealed MSL2's RING as a functional E3 ubiquitin ligase with two distinct roles: histone H2B K34 ubiquitylation driving trans-tail methylation, and homeostatic autoubiquitylation/degradation of excess subunits.

    Evidence In vitro ubiquitylation with reconstituted nucleosomes, MS site mapping, ChIP, RNAi, proteasome inhibition

    PMID:21726816 PMID:23084834 PMID:30930284 PMID:38831503

    Open questions at the time
    • Why nucleosomal substrates are modified poorly versus free histones unresolved
    • Connection between catalytic and scaffolding roles not integrated
  8. 2019 High

    Established CLAMP as a direct MSL2 partner functionally redundant with direct DNA binding, refining the model of how MSL2 is positioned at MREs.

    Evidence Transgenic CBD/CXC double mutants, NMR of CLAMP zinc finger, chromatin reconstitution and CUT&RUN

    PMID:31320325 PMID:35648444 PMID:37602401

    Open questions at the time
    • Relative contributions of CLAMP versus DNA binding across loci not fully quantified
    • How cooperativity is coordinated with roX condensation unknown
  9. 2018 High

    Extended the female repressor complex with Hrp48, HOW, and eIF3d, defining nuclear retention and translation-factor-level control of msl-2.

    Evidence RNAi, RNA chromatography, Co-IP, NMR/ITC, single-molecule kinetics, in vivo genetics

    PMID:23788626 PMID:29635389 PMID:39504588 PMID:bio_10.1101_2025.04.07.647595

    Open questions at the time
    • Integration of multiple co-repressors into one quantitative model incomplete
    • Single-molecule kinetics from preprint not peer-reviewed
  10. 2017 Medium

    Demonstrated mammalian MSL2 functions beyond dosage compensation, acting in DNA repair and as a regulated ubiquitin ligase in viral and neurodevelopmental contexts.

    Evidence DT40 gene disruption with NHEJ assays, 53BP1/APOBEC3B ubiquitylation, conditional KO mice with multi-omics

    PMID:23874665 PMID:28608964 PMID:42168661

    Open questions at the time
    • Whether mammalian roles share the dosage-compensation E3 mechanism unresolved
    • Substrate range in mammals not comprehensively defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MSL2's catalytic E3 ligase activity, DNA/CLAMP-mediated targeting, and roX condensate formation are mechanistically coupled into a single regulated chromosome-wide upregulation event remains unresolved.
  • No unified model linking targeting, condensation, and catalysis
  • Conservation/divergence of mechanism between Drosophila and mammals not fully mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 4 GO:0003723 RNA binding 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-4839726 Chromatin organization 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-73894 DNA Repair 1
Partners
CLAMPMLEMSL1MSL3ROXSXL
Complex memberships
MSL dosage compensation complex (DCC)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 MSL2 (msl-2) is a RING finger protein required for X chromosome dosage compensation in Drosophila males; it colocalizes with MSL1, MSL3, and MLE on the male X chromosome and coimmunoprecipitates with MSL1 from male larval extracts, indicating formation of a dosage compensation protein complex. Coimmunoprecipitation from larval extracts, immunofluorescence colocalization on polytene chromosomes Cell High 7781064
1995 Ectopic expression of msl-2 in females causes assembly of the other MSL dosage compensation regulators on female X chromosomes and decreased female viability, establishing MSL2 as the limiting/organizing component of the dosage compensation complex. Transgenic ectopic expression in Drosophila females, immunofluorescence Cell High 7781064
1995 MSL2 protein contains a RING finger domain that serves as a putative DNA-binding domain; MSL2 binding to the X chromosome requires the other three MSL proteins (MSL1, MSL3, MLE). Sequence analysis, immunofluorescence in msl mutant backgrounds Development Medium 7588059
1995 MSL1, MSL2, MLE, and histone H4Ac16 display coincident sub-nuclear localization in male embryos; loss of any one MSL protein abolishes sub-nuclear localization of the others, demonstrating mutual interdependence for complex assembly starting from early embryogenesis. Immunostaining in embryos lacking individual MSL proteins Mechanisms of Development High 8562424
1997 Sex-lethal (SXL) represses MSL-2 protein production in females by acting synergistically through sequences in both the 5' and 3' UTRs of msl-2 mRNA at the level of translation, not merely splicing. In vivo reporter assays with UTR mutations, genetic analysis in Drosophila Cell High 9182767
1998 MSL2 RING finger domain mediates interaction with MSL1 to nucleate MSL complex assembly; missense mutations in the first zinc-binding site of the RING finger (but not the second) disrupt MSL2-MSL1 interaction and male viability in vivo. MSL1, MSL2, and MSL3 are associated in immunoprecipitations and by yeast two-hybrid, while MLE is only weakly/transiently associated. Yeast two-hybrid, immunoprecipitation, RING finger domain mutagenesis, chromatography The EMBO Journal High 9736618
1999 SXL blocks splicing of the msl-2 intron by binding the polypyrimidine tract and displacing U2AF65, requiring an unusually long distance between the poly(Y) tract and the 3' splice site AG; this combination prevents U2 snRNP binding. U2AF35 contacts the AG dinucleotide and stabilizes U2AF65 binding, making SXL displacement ineffective when AG is proximal. In vitro splicing assays, UV crosslinking, spliceosome assembly assays in HeLa nuclear extracts Nature High 10617208
1999 SXL-mediated translational repression of msl-2 mRNA requires cooperative action of SXL binding sites in both 5' and 3' UTRs and occurs by a poly(A) tail-independent mechanism, demonstrated in a cell-free Drosophila embryo translation system. Cell-free Drosophila embryo translation system, UTR deletion/mutation reporter assays The EMBO Journal High 10545124
2001 SXL binds a uridine-rich sequence downstream of the msl-2 5' splice site and inhibits U1 snRNP recognition of the 5' splice site by antagonizing TIA-1 binding; TIA-1 binding to this sequence is required for U1 snRNP recruitment and splicing of msl-2 pre-mRNA. Psoralen UV crosslinking, in vitro splicing assays, TIA-1 competition experiments in HeLa nuclear extracts RNA High 11565743
2003 SXL inhibits msl-2 mRNA translation at the initiation step by preventing stable association of the 40S ribosomal subunit with the mRNA in a cap-independent manner; both 5' and 3' UTR SXL binding sites contribute to this inhibition. In vitro translation assays, ribosome association assays, UTR mutagenesis Molecular Cell High 12769862
2003 SXL nucleates a co-repressor complex on the msl-2 3' UTR; the RNA-binding and translational repressor functions of SXL map to its two RRM domains and a C-terminal heptapeptide extension. The repressor domain of SXL recruits titratable co-repressor proteins to sequences adjacent to SXL binding sites in the msl-2 3' UTR. Co-immunoprecipitation, UV crosslinking, translation competition assays, tethering assays The EMBO Journal High 14532129
2005 The amino-terminal RING finger domain of MSL2 forms a complex with MSL1 that binds to the heterochromatic chromocenter and a few chromosomal arm sites; incorporation of roX RNAs into the MSL complex requires proline-rich and basic motifs in the MSL2 C-terminal domain and alters the chromatin-binding specificity of the MSL1/MSL2 complex from a few sites to hundreds of X-chromosomal sites. GFP-fusion protein localization in Drosophila, transgenic domain-swap experiments, roX RNA activation assays Molecular and Cellular Biology High 18086881
2005 MSL2 association with the X chromosome in living Drosophila cells (SL2 cells) is exceptionally stable as shown by FRAP (photobleaching); knockdown of MSL2 abolishes H4K16 acetylation and the twofold transcriptional elevation of the X chromosome. Targeting of MSL2 to a reporter gene is sufficient to initiate local dosage compensation. FRAP in living cells, MSL2 RNAi knockdown, transcription assays, reporter gene targeting Chromosoma High 16179989
2006 SXL recruits the ubiquitously expressed protein UNR (upstream of N-ras) specifically to the msl-2 mRNA 3' UTR to act as a co-repressor for 3' UTR-mediated translational regulation, imparting a female-specific function to UNR. Purification of translationally silenced msl-2 mRNPs followed by mass spectrometry identification of UNR; RNAi depletion of UNR; translation reporter assays Genes & Development High 16452508
2009 The SXL-UNR 3' UTR co-repressor complex inhibits ribosome recruitment to msl-2 mRNA via a mechanism requiring the poly(A) tail and PABP function; UNR directly interacts with PABP, and the repressor complex targets ribosome binding after PABP-mediated recruitment of eIF4E/G. Biochemical assays for eIF4F and ribosome recruitment, UNR-PABP interaction assays, poly(A) tail and PABP requirement experiments Molecular Cell High 19941818
2010 The CXC domain of MSL2 directly binds DNA with low nanomolar affinity in vitro; this DNA-binding activity is required for faithful targeting of the dosage compensation complex (DCC) to the X chromosome in vivo, as shown by reporter gene assays and GFP-fusion localization of CXC domain mutants. Recombinant MSL2 DNA-binding assays in vitro, reporter gene assays in vivo, GFP-fusion protein localization Nucleic Acids Research High 20139418
2011 Human MSL2, together with MSL1, functions as a histone ubiquitin E3 ligase that targets nucleosomal H2B on lysine 34 (H2B K34ub); this modification directly regulates H3 K4 and K79 methylation through trans-tail crosstalk both in vitro and in cells, and is important for transcription activation at HOXA9 and MEIS1 loci. In vitro ubiquitylation assays with reconstituted nucleosomes, mass spectrometry identification of H2B K34ub, chromatin immunoprecipitation, RNAi knockdown with transcription assays Molecular Cell High 21726816
2011 MSL2 binds spliced, polyadenylated msl2 mRNA through a non-chromatin-associated partial or complete MSL complex, suggesting a feedback mechanism whereby free MSL complex titrates newly transcribed msl2 mRNA to regulate available MSL complex levels. RNA immunoprecipitation, RT-PCR, characterization of MSL complex-associated RNAs Nucleic Acids Research Medium 21551218
2012 MSL2 is an E3 ubiquitin ligase that ubiquitylates itself and other MSL complex components (including MSL1) when their stoichiometry is unbalanced, targeting them for proteasome-dependent degradation as a homeostatic control mechanism; modification sites on MSL1 were mapped by mass spectrometry. In vitro ubiquitylation assays, mass spectrometry mapping of ubiquitylation sites, proteasome inhibitor experiments, chromatin interaction studies Molecular Cell High 23084834
2012 The CXC domain of MSL2 contains an unusual Zn3Cys9 cluster with three zinc ions coordinated by six terminal and three bridging cysteines, as determined by NMR spectroscopy; the domain exhibits structural homology to pre-SET motifs of histone lysine methyltransferases. NMR spectroscopy, 1H-113Cd correlation experiments for metal-cysteine connectivity determination PLoS One High 23029009
2013 SXL promotes nuclear retention of msl2 mRNA by recruiting the STAR protein HOW to the msl2 5' UTR; HOW directly interacts with SXL and binds two sequence elements in the msl2 5' UTR, cooperating with SXL to retain msl2 transcripts in the nucleus. GRAB (GST pull-down and RNA affinity binding) purification, direct binding assays, HOW RNAi depletion, nuclear retention assays Genes & Development High 23788626
2013 Disruption of the Msl2 gene in chicken DT40 cells reveals a role in DNA damage response: Msl2-/- cells and hMSL2-depleted human cells have defects in non-homologous end joining (NHEJ) repair. hMSL2 is modified and stabilized after DNA damage, and mediates ubiquitylation of 53BP1 at lysine 1690. hMSL1 and hMOF are also modified in the presence of hMSL2 after DNA damage. Gene disruption in DT40 cells, DNA repair assays (NHEJ), immunoblotting for protein modification, site-directed analysis of 53BP1 K1690 PLoS One Medium 23874665
2014 The CXC domain of MSL2 specifically recognizes the MSL recognition element (MRE) motif on the X chromosome; the crystal structure of the CXC domain bound to DNA shows it primarily contacts one strand of the DNA duplex and employs a single arginine to read out dinucleotide sequences from the minor groove. The MRE core region harbors two binding sites on opposite strands that can cooperatively recruit a CXC dimer. Specific DNA-binding mutants are impaired in MRE binding and X chromosome localization in vivo. Crystal structure determination of CXC domain bound to specific and nonspecific DNAs, in vitro DNA binding assays, mutagenesis, in vivo X chromosome localization assays Genes & Development High 25452275
2017 Human MSL2 maintains HBV covalently closed circular DNA (cccDNA) stability in hepatoma cells by ubiquitylating and degrading APOBEC3B, a cytidine deaminase that would otherwise edit/degrade cccDNA. HBx upregulates MSL2 expression via the YAP/FoxA1 signaling pathway, with HBx enhancing FoxA1 binding to the MSL2 promoter at nucleotides -1317/-1167. Ubiquitylation assays for APOBEC3B degradation, luciferase reporter gene assays for MSL2 promoter, chromatin immunoprecipitation (ChIP), siRNA knockdown, HBx-transgenic mouse models Hepatology Medium 28608964
2018 Hrp48 is a SXL co-factor that binds the msl-2 3' UTR and is required for optimal SXL-mediated translational repression; Hrp48 interacts with eIF3d, which binds the msl-2 5' UTR and is required for both efficient translation and translational repression. Depletion of eIF3d (but not other eIF3 subunits) de-represses msl-2 expression in female flies. RNAi depletion, reporter assays, RNA chromatography, co-immunoprecipitation, in vivo genetic depletion Nucleic Acids Research High 29635389
2019 The MSL2 Clamp-Binding Domain (CBD) directly interacts with the N-terminal zinc-finger domain of the ubiquitous DNA-binding protein CLAMP; inactivation of CBD alone or CXC domain alone only modestly affects DCC recruitment to the X chromosome, but combining both mutations causes significant loss of DCC recruitment, demonstrating redundancy between CLAMP interaction and direct DNA binding for MSL2 positioning. Transgenic Drosophila with CBD and CXC domain mutations, immunostaining for DCC localization, genetic epistasis Development High 31320325
2019 MSL1/MSL2-mediated H2B ubiquitylation efficiency depends on substrate configuration; MSL1/2 efficiently ubiquitylate free histone substrates but very poorly modify intact nucleosomes, implying a requirement for nucleosome structural alteration for efficient H2BK34 ubiquitylation. MSL1/2 can deposit two ubiquitin moieties per nucleosome. In vitro ubiquitylation assays with purified MSL1/MSL2, nucleosome gel-mobility shift assays, biochemical substrate comparison Archives of Biochemistry and Biophysics Medium 30930284
2020 The low-complexity C-terminal domain (CTD) of MSL2 renders X chromosome recruitment sensitive to roX non-coding RNAs; roX RNAs and the MSL2 CTD form a stably condensed state (phase separation-like). Replacing the CTD of mammalian MSL2 with that from Drosophila and expressing roX in cis is sufficient to nucleate ectopic dosage compensation in mammalian cells. Functional domain swap experiments in Drosophila and mammalian cells, live imaging of condensate formation, genetic analysis of roX-MSL2 CTD interactions in vivo Nature High 33208948
2022 The intrinsically disordered region of MSL2 specifically interacts with the N-terminal C2H2 zinc-finger domain of CLAMP; the NMR structure of the CLAMP N-terminal C2H2 zinc finger was determined, revealing a classic C2H2 fold with unusual distribution of DNA-recognition residues. This interaction is conserved only within Drosophilidae, suggesting it evolved specifically for DCC recruitment in this genus. NMR structure determination, mutagenesis of CLAMP C2H2 domain, in vivo viability assays Nucleic Acids Research High 35648444
2023 MSL2-CLAMP cooperativity at MRE sites on the X chromosome requires direct physical interaction between the two proteins; disruption of the MSL2-CLAMP interaction does not produce indirect nucleosome-mediated cooperativity but instead causes competition between the two proteins. This cooperativity functions at individual MREs rather than being influenced by MRE clustering. Reconstitution of binding on naïve embryonic chromatin, mutagenesis of interaction interface, DNA binding and competition assays, CUT&RUN for in vivo MSL2 binding Nucleic Acids Research High 37602401
2024 The B-domain (basic amino acid-rich C-terminal domain) of MSL2 destabilizes the MSL2 protein through ubiquitylation of two lysines controlled by its own RING domain; the proline-rich domain (P-domain) stimulates transcription of the roX2 gene, which is necessary for effective formation of the dosage compensation complex. Transgenic Drosophila domain deletion/mutation analysis, protein stability assays, roX2 transcription assays Biochemistry (Biokhimiia) Medium 38831503
2024 Hrp48 binds a specific region of the msl-2 3' UTR downstream of the Sxl and Unr E/F binding sites, independently of Sxl and Unr, as characterized by NMR spectroscopy and isothermal titration calorimetry. Hrp48 further stabilizes RNA-bound Sxl indirectly via ATP-independent RNA remodeling. NMR spectroscopy, molecular dynamics simulations, isothermal titration calorimetry, translation assays Biophysical Chemistry High 39504588
2025 Real-time single-molecule imaging shows that Sxl targets msl-2 mRNA binding sites via sliding and double-binding; Unr recruitment to msl-2 is accelerated over 500-fold by RNA-bound Sxl; Hrp48 further stabilizes RNA-bound Sxl indirectly via ATP-independent RNA remodeling, with these mechanisms synergistically achieving tight translational repression. Multi-color single-molecule fluorescence microscopy, kinetic analysis of mRNP assembly bioRxiv (preprint)preprint Medium bio_10.1101_2025.04.07.647595
2026 Nervous system-specific conditional knockout of Msl2 in mice causes impaired social novelty recognition, learning deficits, and spatial memory impairments, associated with disrupted neocortical lamination, impaired neural progenitor proliferation and differentiation, and reduced neuronal migration. Mechanistically, Msl2-deficient brains show significantly reduced H4K16ac at promoter regions, widespread transcriptional downregulation, and loss of chromatin accessibility at NDD-related genes; MSL2 DNA-binding domain variants disrupted targeting of key regulatory genes including FMR1. Conditional knockout mice, behavioral assays, RNA-seq, ChIP-seq, ATAC-seq, immunostaining Cellular and Molecular Life Sciences High 42168661

Source papers

Stage 0 corpus · 45 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila. Cell 274 7781064
1999 Inhibition of msl-2 splicing by Sex-lethal reveals interaction between U2AF35 and the 3' splice site AG. Nature 247 10617208
1997 The regulation of the Drosophila msl-2 gene reveals a function for Sex-lethal in translational control. Cell 177 9182767
1995 The msl-2 dosage compensation gene of Drosophila encodes a putative DNA-binding protein whose expression is sex specifically regulated by Sex-lethal. Development (Cambridge, England) 145 7588059
2011 The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B K34 and is involved in crosstalk with H3 K4 and K79 methylation. Molecular cell 133 21726816
1999 Translational control of dosage compensation in Drosophila by Sex-lethal: cooperative silencing via the 5' and 3' UTRs of msl-2 mRNA is independent of the poly(A) tail. The EMBO journal 115 10545124
1998 Complex formation by the Drosophila MSL proteins: role of the MSL2 RING finger in protein complex assembly. The EMBO journal 106 9736618
2006 Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3' UTR: translational repression for dosage compensation. Genes & development 76 16452508
2017 Hepatitis B virus X protein-elevated MSL2 modulates hepatitis B virus covalently closed circular DNA by inducing degradation of APOBEC3B to enhance hepatocarcinogenesis. Hepatology (Baltimore, Md.) 65 28608964
1995 The dosage compensation regulators MLE, MSL-1 and MSL-2 are interdependent since early embryogenesis in Drosophila. Mechanisms of development 64 8562424
2009 The SXL-UNR corepressor complex uses a PABP-mediated mechanism to inhibit ribosome recruitment to msl-2 mRNA. Molecular cell 63 19941818
2003 Drosophila sex-lethal inhibits the stable association of the 40S ribosomal subunit with msl-2 mRNA. Molecular cell 60 12769862
2010 The DNA binding CXC domain of MSL2 is required for faithful targeting the Dosage Compensation Complex to the X chromosome. Nucleic acids research 59 20139418
2007 Incorporation of the noncoding roX RNAs alters the chromatin-binding specificity of the Drosophila MSL1/MSL2 complex. Molecular and cellular biology 48 18086881
2005 The amino-terminal region of Drosophila MSL1 contains basic, glycine-rich, and leucine zipper-like motifs that promote X chromosome binding, self-association, and MSL2 binding, respectively. Molecular and cellular biology 47 16199870
2003 A co-repressor assembly nucleated by Sex-lethal in the 3'UTR mediates translational control of Drosophila msl-2 mRNA. The EMBO journal 44 14532129
2020 RNA nucleation by MSL2 induces selective X chromosome compartmentalization. Nature 40 33208948
2005 Stable chromosomal association of MSL2 defines a dosage-compensated nuclear compartment. Chromosoma 33 16179989
2018 The long noncoding RNA MALAT-1 functions as a competing endogenous RNA to regulate MSL2 expression by sponging miR-338-3p in myasthenia gravis. Journal of cellular biochemistry 29 30362606
2012 MSL2 combines sensor and effector functions in homeostatic control of the Drosophila dosage compensation machinery. Molecular cell 29 23084834
2001 Modulation of msl-2 5' splice site recognition by Sex-lethal. RNA (New York, N.Y.) 29 11565743
2014 Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation. Genes & development 26 25452275
1982 Studies on the sex-specific lethals of Drosophila melanogaster. V. Sex transformation caused by interactions between a female-specific lethal, Sxlf 1, and the male-specific lethals mle(3)132, msl-2(27), and mle. Genetics 20 6818105
2019 Genetic and physical interactions between the organellar mechanosensitive ion channel homologs MSL1, MSL2, and MSL3 reveal a role for inter-organellar communication in plant development. Plant direct 19 31245767
2018 Hrp48 and eIF3d contribute to msl-2 mRNA translational repression. Nucleic acids research 19 29635389
2013 Sex-lethal promotes nuclear retention of msl2 mRNA via interactions with the STAR protein HOW. Genes & development 19 23788626
2012 Solution structure of MSL2 CXC domain reveals an unusual Zn3Cys9 cluster and similarity to pre-SET domains of histone lysine methyltransferases. PloS one 18 23029009
1982 Studies on the sex-specific lethals of Drosophila melanogaster. IV. Gynandromorph analysis of three male-specific lethals, mle, msl-2(27) and mle(3)132. Genetics 18 6818104
2011 msl2 mRNA is bound by free nuclear MSL complex in Drosophila melanogaster. Nucleic acids research 17 21551218
1996 Dosage compensation in Drosophila: the X chromosome binding of MSL-1 and MSL-2 in female embryos is prevented by the early expression of the Sxl gene. Mechanisms of development 17 8817458
2019 The simultaneous interaction of MSL2 with CLAMP and DNA provides redundancy in the initiation of dosage compensation in Drosophila males. Development (Cambridge, England) 15 31320325
2022 Structural basis for interaction between CLAMP and MSL2 proteins involved in the specific recruitment of the dosage compensation complex in Drosophila. Nucleic acids research 10 35648444
2024 MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature. American journal of human genetics 9 38815585
2020 IFN-α2b inhibits the ethanol enriched-HBV cccDNA through blocking a positive feedback loop of HBx/MSL2/cccDNA/HBV/HBx in liver. Biochemical and biophysical research communications 9 32446394
2019 Antiviral therapy may decrease HBx, affecting cccDNA and MSL2 in hepatocarcinogenesis. Oncology letters 8 31612010
2023 Physical interaction between MSL2 and CLAMP assures direct cooperativity and prevents competition at composite binding sites. Nucleic acids research 7 37602401
2015 X-to-autosome expression and msl-2 transcript abundance correlate among Drosophila melanogaster somatic tissues. PeerJ 6 25737812
2013 Msl2 is a novel component of the vertebrate DNA damage response. PloS one 6 23874665
2024 The Drosophila RNA binding protein Hrp48 binds a specific RNA sequence of the msl-2 mRNA 3' UTR to regulate translation. Biophysical chemistry 5 39504588
2024 Novel protein-truncating variants of a chromatin-modifying gene MSL2 in syndromic neurodevelopmental disorders. European journal of human genetics : EJHG 4 38702431
2021 In Hepatocellular Carcinoma, miRNA-296-3p Targets MSL2 and Suppresses Cell Proliferation and Invasion. Journal of oncology 4 34899909
2019 Analysis of histone ubiquitylation by MSL1/MSL2 proteins in vitro. Archives of biochemistry and biophysics 4 30930284
2025 Prenatal Diagnosis of MSL2-Related Ventriculomegaly in Association With an Inherited 15q13 Microduplication. Clinical genetics 1 40954079
2024 Functional Role of C-terminal Domains in the MSL2 Protein of Drosophila melanogaster. Biochemistry. Biokhimiia 1 38831503
2026 MSL2 disruption leads to autism-like behaviors, impairs neurogenesis, and alters histone H4K16 acetylation. Cellular and molecular life sciences : CMLS 0 42168661

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