PCGF6-PRC1 suppresses premature differentiation of embryonic stem cells by silencing germ cell-related genes [ChIP-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE87484 | GEO | 2017/03/16
SECONDARY ACCESSION(S): PRJNA344893
REPOSITORIES: GEO
Similar Datasets
Project description:Expression data of ES cells with or without Pcgf6, Ring1A/B, Max and Mga. Expression data of ES cells with or without Cbx1/3.
2017-03-16 | GSE84480 | GEO
Project description:PCGF6-PRC1 suppresses premature differentiation of embryonic stem cells by silencing germ cell-related genes
| PRJNA344891 | ENA
Project description:The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability. We also find a role for PCGF6 in pre- and peri-implantation mouse embryonic development. We further show that a heterodimer of the transcription factors MAX and MGA recruits PCGF6 to target loci. PCGF6 thus links sequence specific target recognition by the MAX/MGA complex to PRC1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells.
| S-EPMC5375644 | biostudies-literature
Project description:We report that the PRC1 component polycomb group ring finger 6 (Pcgf6) is required to maintain embryonic stem cell (ESC) identity. In contrast to canonical PRC1, Pcgf6 acts as a positive regulator of transcription and binds predominantly to promoters bearing active chromatin marks. Pcgf6 is expressed at high levels in ESCs, and knockdown reduces the expression of the core ESC regulators Oct4,Sox2, and Nanog. Conversely, Pcgf6 overexpression prevents downregulation of these factors and impairs differentiation. In addition, Pcgf6 enhanced reprogramming in both mouse and human somatic cells. The genomic binding profile of Pcgf6 is highly similar to that of trithorax group proteins, but not of PRC1 or PRC2 complexes, suggesting that Pcgf6 functions atypically in ESCs. Our data reveal novel roles for Pcgf6 in directly regulating Oct4, Nanog, Sox2, and Lin28 expression to maintain ESC identity. To identify Pcgf6-bound genomic DNA regions in mouse embryonic stem cells, we fixed mouse ESCs and isolated Pcgf6-bound genomic DNA regions for deep sequencing analysis.
2016-07-28 | E-GEOD-84905 | biostudies-arrayexpress
Project description:Polycomb group (PcG) proteins comprise a large group of evolutionary conserved factors with essential roles for embryonic development and adult stem cell function. PcG proteins constitute two main multiprotein polycomb repressive complexes (PRC1 and PRC2) that operate in a hierarchical manner to silence gene expression. Functionally distinct PRC1 complexes are defined by Polycomb group RING finger protein (PCGF) paralogs. So far, six PCGF paralogs (PCGF1-6) have been identified but paralog-specific functions are not well understood. In our studies, we observed that Pcgf6 showed the highest expression level in undifferentiated murine embryonic stem cells (ESCs), blastocysts and testes. When ESCs differentiated, Pcgf6 expression strongly declined. To further investigate Pcgf6 biology, we established dox-inducible shRNA knockdown (KD) ESCs. Following Pcgf6 KD in ESCs the expression of pluripotency genes decreased, while mesodermal- and spermatogenesis-specific genes were de-repressed. Concomitantly with the elevated expression of mesodermal lineage markers, Pcgf6 KD ESCs showed increased hemangioblastic and hematopoietic activities. Finally, PCGF6 replaced SOX2 but not KLF4 or c-MYC in the generation of germline-competent iPS cells. Forced expression of Pcgf6 in OSKM-driven reprogramming increases iPS efficiency while Pcgf6 KD reduces the formation of ESC-like colonies. Together, these analyses show that Pcgf6 is non-redundantly involved in maintaining the pluripotent nature of ESCs and functions in iPS reprogramming. 6 samples were hybridized GeneChip Mouse Gene 1.0 ST Arrays (Affymetrix)
2014-09-26 | E-GEOD-56126 | biostudies-arrayexpress
Project description:The Polycomb group (PcG) proteins have an important role in controlling the expression of key genes implicated in embryonic development, differentiation and decision of cell fates. Emerging evidence suggests that Polycomb repressive complexes 1 (PRC1) is defined by the six Polycomb group RING finger protein (Pcgf) paralogs and Pcgf proteins can assemble into noncanonical PRC1 complexes. However, little is known about the precise mechanisms of differently composed noncanonical PRC1 in the maintenance of the pluripotent cell state. Here we disrupt the Pcgf genes in mouse embryonic stem cells by CRISPR-Cas9 to investigate Pcgf6 function. Microarray experiments were performed using wildtype ,Pcgf6 KO and Pcgf6 KO + Pcgf6_flag ES cells.
2017-01-14 | GSE92476 | GEO
Project description:Polycomb group (PcG) proteins are essential for maintenance of lineage fidelity by coordinating developmental gene expression programs. Polycomb group protein Pcgf6 has been previously reported to repress lineage-specific genes, especially germ cell-related genes in mouse embryonic stem cells (ESCs) via the non- canonical Polycomb repressive complex PRC1. 6. However, the potential mechanism of this repressive activity remains largely unknown. Here, we demonstrated that Pcgf6 played an essential role in embryonic development as indicated by the partially penetrant embryonic lethality in homozygous mice. Additionally, we found that surviving Pcgf6-deficient mice exhibited compromised fertility. Using the Pcgf6 mutant mice, we revealed that ablation of Pcgf6 in somatic tissues also led to robust derepression of such germ cell-related genes. We provided evidence that these genes were direct targets of Pcgf6 in ESCs and endogenous Pcgf6 colocalized with G9a/Glp and Hdac1/2 on the promoters of these germ cell-related genes and that binding of these proteins to target genes correlated with methylation of H3K9 and the status of histone acetylation. Moreover, the recruitment of G9a/Glp and Hdac1/2 to target promoters was dependent on the binding of Pcgf6. Therefore, our study demonstrated a critical role for Pcgf6 in safeguarding lineage decisions and in protecting germ cell-related genes against aberrant expression.
2020-06-16 | GSE143206 | GEO
Project description:Purpose: The goals of this study are to compare Mga-/-, L3mbtl2-/-, Pcgf6-/- and Wild type embryonic stem cells transcriptome profiling (RNA-seq) and compare the target genes of Mga, L3mbtl2 and Pcgf6.
2021-01-21 | GSE144141 | GEO
Project description:We report that the PRC1 component polycomb group ring finger 6 (Pcgf6) is required to maintain embryonic stem cell (ESC) identity. In contrast to canonical PRC1, Pcgf6 acts as a positive regulator of transcription and binds predominantly to promoters bearing active chromatin marks. Pcgf6 is expressed at high levels in ESCs, and knockdown reduces the expression of the core ESC regulators Oct4,Sox2, and Nanog. Conversely, Pcgf6 overexpression prevents downregulation of these factors and impairs differentiation. In addition, Pcgf6 enhanced reprogramming in both mouse and human somatic cells. The genomic binding profile of Pcgf6 is highly similar to that of trithorax group proteins, but not of PRC1 or PRC2 complexes, suggesting that Pcgf6 functions atypically in ESCs. Our data reveal novel roles for Pcgf6 in directly regulating Oct4, Nanog, Sox2, and Lin28 expression to maintain ESC identity.
2016-07-28 | GSE84905 | GEO
Project description:Polycomb group (PcG) proteins comprise a large group of evolutionary conserved factors with essential roles for embryonic development and adult stem cell function. PcG proteins constitute two main multiprotein polycomb repressive complexes (PRC1 and PRC2) that operate in a hierarchical manner to silence gene expression. Functionally distinct PRC1 complexes are defined by Polycomb group RING finger protein (PCGF) paralogs. So far, six PCGF paralogs (PCGF1-6) have been identified but paralog-specific functions are not well understood. In our studies, we observed that Pcgf6 showed the highest expression level in undifferentiated murine embryonic stem cells (ESCs), blastocysts and testes. When ESCs differentiated, Pcgf6 expression strongly declined. To further investigate Pcgf6 biology, we established dox-inducible shRNA knockdown (KD) ESCs. Following Pcgf6 KD in ESCs the expression of pluripotency genes decreased, while mesodermal- and spermatogenesis-specific genes were de-repressed. Concomitantly with the elevated expression of mesodermal lineage markers, Pcgf6 KD ESCs showed increased hemangioblastic and hematopoietic activities. Finally, PCGF6 replaced SOX2 but not KLF4 or c-MYC in the generation of germline-competent iPS cells. Forced expression of Pcgf6 in OSKM-driven reprogramming increases iPS efficiency while Pcgf6 KD reduces the formation of ESC-like colonies. Together, these analyses show that Pcgf6 is non-redundantly involved in maintaining the pluripotent nature of ESCs and functions in iPS reprogramming.
2014-09-26 | GSE56126 | GEO