| 1999 |
MORC1 (mouse Morc) encodes a 108 kDa nuclear protein required for spermatogenesis; it contains putative nuclear localization signals, two coiled-coil motifs, and limited homology to GHL ATPases. Epitope-tagged MORC localizes to the nucleus in COS7 cells. Loss of function (transgenic insertional mutation removing exons 2–4) causes arrest of spermatogenesis prior to the pachytene stage of meiosis prophase I. |
Positional cloning, transgenic insertional mutagenesis, epitope-tag nuclear localization in COS7 cells, immunofluorescence with synaptonemal complex antigens, apoptosis assay |
Human molecular genetics |
High |
10369865
|
| 1998 |
Male mice homozygous for the morc loss-of-function mutation fail to progress beyond zygotene/leptotene stage of meiosis prophase I, with massive apoptosis in testes; females are unaffected, indicating MORC1 acts specifically during male gametogenesis. |
Autosomal recessive mouse genetics, immunofluorescence to synaptonemal complex antigens, TUNEL apoptosis assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
9826705
|
| 2014 |
Mouse MORC1 is required for transposon repression in the male germline; Morc1 mutants show highly localized defects in the establishment of DNA methylation at specific classes of transposons (resembling DNMT3L-deficient germ cells), and these methylation defects are associated with failed transposon silencing at those sites. |
Morc1 knockout mouse, bisulfite sequencing for DNA methylation, RNA-seq for transposon expression, comparison to Dnmt3l mutants |
Nature communications |
High |
25503965
|
| 2024 |
In mouse gonocytes, MORC1 cooperates with the H3K9me3 methyltransferase SETDB1 to deposit repressive H3K9me3 on a large fraction of activated transposable elements, re-establishing heterochromatin. MORC1-driven DNA methylation targets only slightly overlap with those repressed by the MORC1/SETDB1 heterochromatin pathway, indicating MORC1 silences TEs by two distinct mechanisms. MORC1 targets almost completely overlap with MIWI2 (nuclear PIWI) targets, suggesting MIWI2/piRNAs select targets while MORC1 acts downstream to repress them. |
Morc1 knockout mouse, ChIP-seq (H3K9me3), bisulfite sequencing, genetic epistasis with Miwi2 and Setdb1 mutants, RNA-seq |
Proceedings of the National Academy of Sciences of the United States of America |
High |
38502704
|
| 2017 |
In C. elegans, MORC-1 acts as a downstream effector of germline endo-siRNAs (nuclear RNAi pathway); it is dispensable for siRNA inheritance but required for target gene silencing and maintenance of siRNA-dependent H3K9me3 chromatin organization. Suppressor screen identified met-1 (H3K36 methyltransferase) mutations as potent suppressors of morc-1 loss-of-function phenotypes, placing MET-1-mediated euchromatin encroachment as the consequence of losing MORC-1 activity. |
C. elegans morc-1 null mutants, forward genetic suppressor screen, ChIP-seq (H3K9me3, H3K36me3), RNA-seq, epistasis analysis |
Developmental cell |
High |
28535375
|
| 2019 |
C. elegans MORC-1 binds DNA in a length-dependent but sequence-non-specific manner, compacts DNA by forming loops, diffuses along DNA and becomes static as it grows into topologically entrapped foci, forms multimeric assemblies, and can form phase-separated droplets in vitro. MORC-1 also compacts nucleosome templates. In vivo, MORC-1 forms nuclear puncta. |
Single-molecule imaging, biochemical DNA-binding assays, in vitro phase separation assay, atomic force microscopy, live-cell fluorescence imaging, nucleosome compaction assay |
Molecular cell |
High |
31442422
|
| 2022 |
In Arabidopsis, the catalytic subunit of DNA polymerase epsilon (POL2A) interacts via its N-terminus with MORC1's GHKL ATPase domain and is required for MORC1 localization on meiotic heterochromatin; loss of the POL2A N-terminus causes aberrant meiotic heterochromatin morphology phenocopying morc1 mutants. The POL2A C-terminal zinc finger (ZF1) binds histone H3.1-H4 dimer/tetramer and the mouse POL2A counterpart shows similar H3.1-binding specificity, suggesting conservation. |
Co-immunoprecipitation, yeast two-hybrid, Arabidopsis mutant analysis (pol2a, morc1), ChIP, histone-binding assay, genetic epistasis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
36260743
|
| 2025 |
In C. elegans, MORC-1 is a direct slicing target of CSR-1 (Argonaute); over-accumulation of MORC-1 in csr-1 mutants drives ectopic H3K9me3 gain, H3K36me3 loss, and transcriptional repression of CSR-1-licensed germline targets. Loss of morc-1 fully rescues these chromatin defects in csr-1 mutants, and ectopic overexpression of MORC-1 in wild-type germline is sufficient to repress CSR-1 targets and cause sterility. |
C. elegans genetics (morc-1 and csr-1 single/double mutants), MORC-1 overexpression transgenics, ChIP-seq (H3K9me3, H3K36me3), RNA-seq, genetic epistasis |
Science advances |
High |
40540580
|
| 2017 |
Plant and human MORC proteins exhibit topoisomerase II-like DNA modification activities: they covalently bind DNA, show DNA-stimulated ATPase activity, relax or nick supercoiled DNA, catenate DNA, and decatenate kinetoplast DNA. Mutational analysis of tomato SlMORC1 showed that a K loop-like sequence is required to couple DNA binding to ATPase stimulation and for DNA relaxation and catenation activities. Both plant and human MORCs bind salicylic acid, which suppresses their decatenation but not relaxation activity. |
In vitro topoisomerase assays (relaxation, catenation, decatenation of kDNA), ATPase assay, covalent DNA-binding assay, site-directed mutagenesis, salicylic acid binding/inhibition assay |
Molecular plant-microbe interactions : MPMI |
High |
27992291
|
| 2024 |
A conserved catalytic lysine residue in the GHKL ATPase domain is critical for ATPase activity in MORC family proteins; this residue is confirmed to be conserved among MORC, MutL, and DNA gyrase GHKL ATPases, indicating a shared catalytic mechanism within the superfamily. |
Site-directed mutagenesis of ATPase domain, ATPase kinetic assays (pH dependence), analysis of human MutL homolog mutants |
Journal of molecular biology |
Medium |
38641238
|
| 2015 |
The C-terminal region of solanaceous MORC1 proteins determines species-specific effects on immunity-related cell death and is required for homodimerization and phosphorylation of recombinant StMORC1 and SlMORC1. Domain-swapping and mutagenesis demonstrated this region's role in modulating biological activity. |
Domain-swapping constructs, site-directed mutagenesis, in vitro phosphorylation assay, dimerization assay, transient expression in N. benthamiana (plant cell death assay) |
Molecular plant-microbe interactions : MPMI |
Medium |
25822715
|
| 2025 |
C. elegans MORC-1 is regulated by CSR-1's slicer/endonuclease activity (morc-1 mRNA is a direct slicer target), such that CSR-1 prevents MORC-1 overexpression; this regulation is essential for preventing MORC-1-mediated repression of CSR-1-licensed germline genes. (Preprint version of PMID:40540580.) |
C. elegans genetics, MORC-1 overexpression transgenics, ChIP-seq, RNA-seq, genetic epistasis |
bioRxivpreprint |
Medium |
bio_10.1101_2024.10.02.616347
|