ArticleThe Journal of biological chemistry2009
Epigenetic gene silencing by the SRY protein is mediated by a KRAB-O protein that recruits the KAP1 co-repressor machinery.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 73 citations in OpenAlex.
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- Using High-Throughput Measurements to Identify Principles of Transcriptional and Epigenetic Regulators.Methods in molecular biology (Clifton, N.J.) · 2024Article
- B1 SINE-binding ZFP266 impedes mouse iPSC generation through suppression of chromatin opening mediated by reprogramming factors.Nature communications · 2023Article
- Structure and functional mapping of the KRAB-KAP1 repressor complex.The EMBO journal · 2022Article
- Mapping the interaction between Trim28 and the KRAB domain at the center of Trim28 silencing of endogenous retroviruses.Protein science : a publication of the Protein Society · 2022Article
- TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway.Nature communications · 2022Article
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- The KRAB Domain of ZNF10 Guides the Identification of Specific Amino Acids That Transform the Ancestral KRAB-A-Related Domain Present in Human PRDM9 into a Canonical Modern KRAB-A Domain.International journal of molecular sciences · 2022Article
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- ZNF354C is a transcriptional repressor that inhibits endothelial angiogenic sprouting.Scientific reports · 2020Article
- MIPPIE: the mouse integrated protein-protein interaction reference.Database : the journal of biological databases and curation · 2020Article
- In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression.Journal of visualized experiments : JoVE · 2019Article
- Epigenetic regulation of male fate commitment from an initially bipotential system.Molecular and cellular endocrinology · 2018Review
- A novel association of campomelic dysplasia and hydrocephalus with an unbalanced chromosomal translocation upstream ofCold Spring Harbor molecular case studies · 2018Article
- Characterization of Coding/Noncoding Variants forJournal of the American Society of Nephrology : JASN · 2018Article
- Familial and SomaticCancer research · 2018Article
- The REMOTE-control system: a system for reversible and tunable control of endogenous gene expression in mice.Nucleic acids research · 2017Article
- Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice.Scientific reports · 2017Article
- Chromosome Y genetic variants: impact in animal models and on human disease.Physiological genomics · 2015Review
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
The sex determination transcription factor SRY is a cell fate-determining transcription factor that mediates testis differentiation during embryogenesis. It may function by repressing the ovarian determinant gene, RSPO1, action in the ovarian developmental pathway and activates genes, such as SOX9, important for testis differentiation at the onset of gonadogenesis. Further, altered expression of SRY and related SOX genes contribute to oncogenesis in many human cancers. Little is known of the mechanisms by which SRY regulates its target genes. Recently a KRAB domain protein (KRAB-O) that lacks a zinc finger motif has been demonstrated to interact with SRY and hypothesized to function as an adaptor molecule for SRY by tethering the KAP1-NuRD-SETDB1-HP1 silencing machinery to repress SRY targets. We have critically examined this hypothesis by reconstituting and characterizing SRY-KRAB-O-KAP1 interactions. These recombinant molecules can form a ternary complex by direct and high affinity interactions. The KRAB-O protein can simultaneously bind KAP1 and SRY in a noncompetitive but also noncooperative manner. An extensive mutagenesis analysis suggests that different surfaces on KRAB-O are utilized for these independent interactions. Transcriptional repression by SRY requires binding to KRAB-O, thus bridging to the KAP1 repression machinery. This repression machinery is recruited to SRY target promoters in chromatin templates via SRY. These results suggest that SRY has co-opted the KRAB-O protein to recruit the KAP1 repression machinery to sex determination target genes. Other KRAB domain proteins, which lack a zinc finger DNA-binding motif, may function in similar roles as adaptor proteins for epigenetic gene silencing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.