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PCGF6 activates SOX2 and contributes to lineage differentiation of human pluripotent stem cells

ABSTRACT: To assess and distinguish the molecular role of PCGF6 in the self-renewal and early differentiation of PSCs, we established PCGF6-knockout PSCs. Although the absence of PCGF6 could maintain self-renewal and colony-formation capacity, it induced abnormal early differentiation in PSCs. PCGF6 deficiency in PSCs promoted the development of mesendoderm, and impaired the development of neuroectoderm during differentiation process in vitro. RNA-seq and ChIP-seq experiments revealed that PCGF6 plays different roles in distinct lineage specification. On the one hand, PCGF6 worked as a transcription activator that maintain early neuroectoderm differentiation by regulating the expression of SOX2. On the other hand, PCGF6 resists skewed differentiation toward mesendoderm through the PRC1-dependent inhibition of WNT/β-catenin signaling pathways.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173690 | GEO | 2022/07/16

REPOSITORIES: GEO

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Polycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity

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.Â Pcgf6Â is expressed at high levels in ESCs, and knockdown reduces the expression of the core ESC regulatorsÂ Oct4,Sox2, andÂ Nanog. Conversely,Â Pcgf6Â 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 regulatingÂ Oct4,Â Nanog,Â Sox2, andÂ 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

Polycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity

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

Expression regulation by Pcgf6 in mouse embryonic stem cells

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2017-01-14 | GSE92476 | GEO

PCGF6, a polycomb group protein, regulates mesodermal lineage differentiation in murine ES cells and functions in iPS reprogramming

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2021-12-05 | GSE189999 | GEO

Pcgf6 suppresses Myc-induced lymphomagenesis [ChIP-seq]

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RNA-seq for the tissues of Pcgf6 knockout mice and wild type mice

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

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2016-07-13 | GSE83640 | GEO

Pcgf6 suppresses Myc-induced lymphomagenesis

Project description:Pcgf6 suppresses Myc-induced lymphomagenesis

| PRJNA785557 | ENA

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2023-12-18 | GSE228479 | GEO

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