Polycomb Repressive Complex 2 (PRC2) plays an essential role in gene repression during development, catalyzing H3 lysine 27 trimethylation (H3K27me3). MTF2 in the PRC2.1 sub-complex, and JARID2 in PRC2.2, are central in core PRC2 recruitment to target genes in mouse embryonic stem cells (mESCs). To investigate how PRC2.1 and PRC2.2 cooperate, we combined Polycomb mutant mESCs with chemical inhibition of binding to H3K27me3. We find that PRC2.1 and PRC2.2 mediate two distinct paths for recruitment, which are mutually reinforced. Whereas PRC2.1 recruitment is mediated by MTF2 binding to DNA, JARID2-containing PRC2.2 recruitment is more dependent on PRC1. Both recruitment axes are supported by core subunit EED binding to H3K27me3, but EED inhibition exhibits a more pronounced effect in Jarid2 null cells. Finally, we show that PRC1 and PRC2 enhance reciprocal binding. Together, these data disentangle the interdependent interactions that are important for PRC2 recruitment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724473 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2020.07.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Gestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2.
Nat Commun
January 2025
College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, 266109, People's Republic of China.
Gestational diabetes mellitus (GDM), a common pregnancy disease, has long-term negative effects on offspring health. Epigenetic changes may have important contributions to that, but the underlying mechanisms are not well understood. Here, we report the influence of GDM on DNA methylation of offspring (GDF1) oocytes and the possible mechanisms.
View Article and Find Full Text PDFSP140 represses specific loci by recruiting polycomb repressive complex 2 and NuRD complex.
Nucleic Acids Res
December 2024
IFOM ETS, The AIRC Institute of Molecular Oncology, Via Adamello 16, 16039 Milano, Italy.
SP140, a lymphocytic-restricted protein, is an epigenetic reader working as a corepressor of genes implicated in inflammation and orchestrating macrophage transcriptional programs to maintain cellular identity. Reduced SP140 expression is associated both to autoimmune diseases and blood cancers. However, the molecular mechanisms that link SP140 altered protein levels to detrimental effects on the immune response and cellular growth, as well as the interactors through which SP140 promotes gene silencing, remain elusive.
View Article and Find Full Text PDFInterchromosomal contacts between regulatory regions trigger stable transgenerational epigenetic inheritance in Drosophila.
Mol Cell
December 2024
Institute of Human Genetics, CNRS and University of Montpellier, 141 Rue de la Cardonille, 34094 Montpellier, France. Electronic address:
Non-genetic information can be inherited across generations in a process known as transgenerational epigenetic inheritance (TEI). In Drosophila, hemizygosity of the Fab-7 regulatory element triggers inheritance of the histone mark H3K27me3 at a homologous locus on another chromosome, resulting in heritable epigenetic differences in eye color. Here, by mutating transcription factor binding sites within the Fab-7 element, we demonstrate the importance of the proteins pleiohomeotic and GAGA factor in the establishment and maintenance of TEI.
View Article and Find Full Text PDFDownregulation of MLF1 safeguards cardiomyocytes against senescence-associated chromatin opening.
Nucleic Acids Res
December 2024
Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen 518057, China.
Aging-associated cardiac hypertrophy (AACH) increases susceptibility to heart failure in the elderly. Chromatin remodeling contributes to the gene reprogramming in AACH; however, the intrinsic regulations remain elusive. We performed a transcriptome analysis for AACH in comparison with pressure-overload-induced pathological cardiac hypertrophy in mice and identified myeloid leukemia factor 1 (MLF1) as an aging-sensitive factor whose expression was reduced during aging but could be reversed by anti-aging administrations.
View Article and Find Full Text PDFDNA hypomethylation promotes UHRF1-and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states.
Mol Cell
November 2024
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA. Electronic address:
Mono-ubiquitination of lysine 18 on histone H3 (H3K18ub), catalyzed by UHRF1, is a DNMT1 docking site that facilitates replication-coupled DNA methylation maintenance. Its functions beyond this are unknown. Here, we genomically map simultaneous increases in UHRF1-dependent H3K18ub and SUV39H1/H2-dependent H3K9me3 following DNMT1 inhibition.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!