Polycomb group (PcG) proteins mediate heritable but reversible silencing of developmental regulator genes by modifying their chromatin configuration. Accumulating evidence documents a role for PcG proteins in regulating higher order chromatin structures likely by their clustering, however, underlying mechanisms and its impact on transcriptional regulation remain obscure. In this study, we found that subnuclear clustering of PRC1 at canonical PcG target genes depended on head-to-tail polymerization property of SAM domain of Phc2 and likely Phc1. We show that Phc2-SAM polymerization limits the dynamic nature of PRC1, thereby promotes stable association of PRC1 with PcG target genes and contributes to their robust silencing. Our findings suggest a novel model by which SAM polymerization of Phc2 modulates the structural organization of PcG complexes to enable robust yet reversible PcG-mediated repression during development.
SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing.
Specimen part, Disease
View SamplesPolycomb group (PcG) proteins mediate heritable but reversible silencing of developmental regulator genes by modifying their chromatin configuration. Accumulating evidence documents a role for PcG proteins in regulating higher order chromatin structures likely by their clustering, however, underlying mechanisms and its impact on transcriptional regulation remain obscure. In this study, we found that subnuclear clustering of PRC1 at canonical PcG target genes depended on head-to-tail polymerization property of SAM domain of Phc2 and likely Phc1. We show that Phc2-SAM polymerization limits the dynamic nature of PRC1, thereby promotes stable association of PRC1 with PcG target genes and contributes to their robust silencing. Our findings suggest a novel model by which SAM polymerization of Phc2 modulates the structural organization of PcG complexes to enable robust yet reversible PcG-mediated repression during development.
SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing.
No sample metadata fields
View SamplesTwo distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3) respectively. Compared to H3K27me3, localization and role of H2AK119ub1 is not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation.
Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity.
Specimen part, Cell line, Treatment
View SamplesWe used microarrays to investigate the restoration of repression of PRC1 target gene expression in Ring1A/B-dKO ES cells stably expressing either of mock, WT or mutant Ring1B construct.
Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity.
Specimen part, Treatment
View SamplesThe CCR4-NOT complex, bearing poly(A) deadenylation activity, is a highly conserved regulator that is involved in biological control; however its action mechanisms and physiological targets remain unclear. Using genetic deletion of the CNOT3 subunit of this complex in early B cell progenitors, we show that CNOT3 plays a critical role in pro- to pre-B cell transition. CNOT3 participated in controlling germline transcription, compaction of the immunoglobulin heavy chain (Igh) locus, and Igh rearrangement, and in destabilizing tumor suppressor p53 mRNA. Moreover, by genetic ablation of p53 or introduction of pre-rearranged Igh transgene, the B cell developmental defect in the Cnot3 knockout background could be partly rescued, suggesting that CCR4-NOT complex exerts critical control in B cell differentiation processes by co-utilizing transcriptional and post-transcriptional mechanisms. Overall design: Pro-B cells mRNA profiles of Mb1(cre/+) and Cnot3(fl/fl)Mb1(cre/+) mice were generated by deep sequencing using Illumina HiSeq 1500
CNOT3 contributes to early B cell development by controlling Igh rearrangement and p53 mRNA stability.
No sample metadata fields
View SamplesEPC1/TIP60-mediated histone acetylation facilitates spermiogenesis in mice Overall design: Gene expression was analyzed using WT and deficient mice for both Epc1 and Epc2.
EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice.
Cell line, Subject
View SamplesGene expression profiling reveals a potential role of Iso towards hepatic differentiation of hAECs.
Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells.
Specimen part
View SamplesGene expression profiling reveals functional difference between Sq and HH-Sq on differentiation, metabolism, and lipid droplot formation of dADSC
New Amphiphilic Squalene Derivative Improves Metabolism of Adipocytes Differentiated From Diabetic Adipose-Derived Stem Cells and Prevents Excessive Lipogenesis.
Specimen part, Disease, Disease stage
View SamplesGene expression profiling reveals a potential role of TCQA in neuronal and pigment cell differentiation of hAECs.
Regulating cell fate of human amnion epithelial cells using natural compounds: an example of enhanced neural and pigment differentiation by 3,4,5-tri-O-caffeoylquinic acid.
Specimen part, Treatment, Time
View SamplesGene expression profiling of the effect of Cyanidine 3 glucoside treatment in hAECs.
Human Amniotic Epithelial Cells as a Tool to Investigate the Effects of Cyanidin 3-<i>O</i>-Glucoside on Cell Differentiation.
Specimen part
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