Tip5/Baz2a Regulates Chromatin Architecture and Gene Expression to Maintain Self-renewal and Pluripotency of Embryonic Stem Cells.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE70975 | GEO | 2016/07/14
SECONDARY ACCESSION(S): PRJNA290269
REPOSITORIES: GEO
Similar Datasets
Project description:It is unclear how gene networks that regulate self-renewal and pluripotency of embryonic stem (ES) cells are established. We searched for factors that contribute to forming functional chromatin architecture in ES cells and identified Tip5 (also called Baz2a) as a genome organizer, folding chromatin and recruiting chromatin remodeling/epigenetic factors to genes. Tip5 binds specialized genomic sequences called base-unpairing regions (BURs) and localizes near heterochromatin. Through chromatin looping Tip5 recruits the polycomb-repressive complex 2 (PRC2) subunits and Jarid2 to target genes far from Tip5-bound BURs and alters their histone profiles. In ES cells Tip5 represses PRC2-bound developmental genes and regulates non-PRC2-bound genes that are enriched for G-protein coupled receptor signaling. Tip5 knockdown caused misexpression of these genes important for ES cell maintenance, leading to rapid ES cell differentiation and impaired pluripotency. These data suggest that Tip5 regulates multiple processes through ES cell-specific genome organization to maintain ES cell stemness.
2016-07-14 | GSE70969 | GEO
Project description:It is unclear how gene networks that regulate self-renewal and pluripotency of embryonic stem (ES) cells are established. We searched for factors that contribute to forming functional chromatin architecture in ES cells and identified Tip5 (also called Baz2a) as a genome organizer, folding chromatin and recruiting chromatin remodeling/epigenetic factors to genes. Tip5 binds specialized genomic sequences called base-unpairing regions (BURs) and localizes near heterochromatin. Through chromatin looping Tip5 recruits the polycomb-repressive complex 2 (PRC2) subunits and Jarid2 to target genes far from Tip5-bound BURs and alters their histone profiles. In ES cells Tip5 represses PRC2-bound developmental genes and regulates non-PRC2-bound genes that are enriched for G-protein coupled receptor signaling. Tip5 knockdown caused misexpression of these genes important for ES cell maintenance, leading to rapid ES cell differentiation and impaired pluripotency. These data suggest that Tip5 regulates multiple processes through ES cell-specific genome organization to maintain ES cell stemness.
2016-07-14 | GSE70974 | GEO
Project description:Self-renewal and pluripotency of embryonic stem (ES) cells are maintained by several signaling cascades and by expression of intrinsic factors, such as Oct4, Nanog and Sox2. The mechanism regulating these signaling cascades in ES cells is of great interest. Recently, we have demonstrated that natriuretic peptide receptor A (NPR-A), a specific receptor for atrial and brain natriuretic peptides (ANP and BNP, respectively), is expressed in pre-implantation embryos and in ES cells. Here, we examined whether NPR-A is involved in the maintenance of ES cell pluripotency. RNA interference-mediated knockdown of NPR-A resulted in phenotypic changes, indicative of differentiation, downregulation of pluripotency factors (such as Oct4, Nanog and Sox2) and upregulation of differentiation genes. NPR-A knockdown also resulted in a marked downregulation of phosphorylated Akt. Furthermore, NPR-A knockdown induced accumulation of ES cells in the G1 phase of the cell cycle. Interestingly, we found that ANP was expressed in self-renewing ES cells, whereas its level was reduced after ES cell differentiation. Treatment of ES cells with ANP upregulated the expression of Oct4, Nanog and phosphorylated Akt, and this upregulation depended on NPR-A signaling, because it was completely reversed by pretreatment with either an NPR-A antagonist or a cGMP-dependent protein kinase inhibitor. These findings provide a novel role for NPR-A in the maintenance of self-renewal and pluripotency of ES cells.
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Project description:Tip5/Baz2a Regulates Chromatin Architecture and Gene Expression to Maintain Self-renewal and Pluripotency of Embryonic Stem Cells.
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