Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE143206 | GEO | 2020/06/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ZFP462 safeguards neural lineage specification by targeting G9A/GLP-mediated heterochromatin to silence enhancers

Project description:ZNF462 haploinsufficiency is linked to Weiss-Kruszka Syndrome, a genetic disorder characterized by neurodevelopmental defects including Autism. Though conserved in vertebrates and essential for embryonic development the molecular functions of ZNF462 remain unclear. We identified its murine homolog ZFP462 in a screen for mediators of epigenetic gene silencing. Here, we show that ZFP462 safeguards neural lineage specification of mouse embryonic stem cells (ESCs) by targeting the H3K9-specific histone methyltransferase complex G9A/GLP to silence mesoendodermal genes. ZFP462 binds to transposable elements (TEs) that are potential enhancers harboring ESC-specific transcription factor (TF) binding sites. Recruiting G9A/GLP, ZFP462 seeds heterochromatin, restricting TF binding. Loss of ZFP462 in ESCs results in increased chromatin accessibility at target sites and ectopic expression of mesoendodermal genes. Taken together, ZFP462 confers lineage- and locus-specificity to the broadly expressed epigenetic regulator G9A/GLP. Our results suggest that aberrant activation of lineage non-specific genes in the neuronal lineage underlies ZNF462-associated neurodevelopmental pathology.

2023-05-10 | PXD037238 | Pride

DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell-related genes in mouse embryonic stem cells

Project description:In embryonic stem cells (ESCs), the expression of development-related genes, including germ cell-related genes, is globally repressed. The transcription factor MAX represses germ cell-related gene expression in ESCs via PCGF6-polycomb repressive complex (PRC)1, which consists of several epigenetic factors. However, we predicted that MAX represses germ cell-related gene expression through several additional mechanisms because PCGF6-PRC1 regulates the expression of only a subset of genes repressed by MAX. Here, we report that MAX associated with DNA methyltransferases (DNMTs) and the histone methyltransferase SETDB1 cooperatively control germ cell-related gene expression in ESCs. Both DNA methylation and histone H3 lysine 9 tri-methylation of the promoter regions of several germ cell-related genes were not affected by knockout of the PRC1 components, indicating that the MAX-DNMT and MAX-SETDB1 pathways are independent of the PCGF6-PRC1 pathway. Our findings provide insights into our understanding of MAX-based repressive mechanisms of germ cell-related genes in ESCs.

2018-08-31 | GSE102610 | GEO

DNA microarray analysis of G9a knockout embryonic stem cells

Project description:In embryonic stem cells (ESCs), the expression of development-related genes, including germ cell–related genes, is globally repressed. The transcription factor MAX represses germ cell–related gene expression in ESCs via PCGF6-polycomb repressive complex (PRC)1, which consists of several epigenetic factors. However, we predicted that MAX represses germ cell–related gene expression through several additional mechanisms because PCGF6-PRC1 regulates the expression of only a subset of genes repressed by MAX. Here, we report that MAX associated with DNA methyltransferases (DNMTs) and the histone methyltransferase SETDB1 cooperatively control germ cell–related gene expression in ESCs. Both DNA methylation and histone H3 lysine 9 tri-methylation of the promoter regions of several germ cell–related genes were not affected by knockout of the PRC1 components, indicating that the MAX-DNMT and MAX-SETDB1 pathways are independent of the PCGF6-PRC1 pathway. Our findings provide insights into our understanding of MAX-based repressive mechanisms of germ cell–related genes in ESCs.

2018-11-10 | GSE102423 | GEO

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

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

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

2014-09-26 | GSE56126 | GEO

ZFP462 safeguards neural lineage specification by targeting G9A/GLP mediated heterochromatin to silence enhancers [QuantSeq]

Project description:ZNF462 haploinsufficiency is linked to Weiss–Kruszka syndrome, a genetic disorder characterized by neurodevelopmental defects, including autism. Though conserved in vertebrates and essential for embryonic development, the molecular functions of ZNF462 remain unclear. We identified its murine homologue ZFP462 in a screen for mediators of epigenetic gene silencing. Here we show that ZFP462 safeguards neural lineage specification of mouse embryonic stem cells (ESCs) by targeting the H3K9-specific histone methyltransferase complex G9A/GLP to silence meso-endodermal genes. ZFP462 binds to transposable elements that are potential enhancers harbouring ESC-specific transcription factor binding sites. Recruiting G9A/GLP, ZFP462 seeds heterochromatin, restricting transcription factor binding. Loss of ZFP462 in ESCs results in increased chromatin accessibility at target sites and ectopic expression of meso-endodermal genes. Taken together, ZFP462 confers lineage and locus specificity to the broadly expressed epigenetic regulator G9A/GLP. Our results suggest that aberrant activation of lineage non-specific genes in the neuronal lineage underlies ZNF462-associated neurodevelopmental pathology.

2023-01-04 | GSE176319 | GEO

ZFP462 safeguards neural lineage specification by targeting G9A/GLP mediated heterochromatin to silence enhancers

2023-01-04 | GSE175369 | GEO