Tip5/Baz2a Regulates Chromatin Architecture and Gene Expression to Maintain Self-renewal and Pluripotency of Embryonic Stem Cells.
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PROVIDER: PRJNA290269 | ENA |
REPOSITORIES: ENA
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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:Elucidating the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can interact with the replication licensing factor MCM2 and inhibit the p53 pathway to maintain the self-renewal and pluripotency of hPSCs. In addition to MCM2, RNA pull-down mass spectrometry showed that ESRG could also bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we show that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG binds to and stabilizes HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encodes E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency.
2024-03-05 | GSE236745 | GEO
Project description:ESRG regulates alternative splicing of TCF3 to maintain hESCs self-renewal and pluripotency
| PRJNA992127 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-07-14 | GSE70975 | GEO
Project description:Chromosomes have an intrinsic tendency to segregate into compartments, forming long-distance contacts between loci of similar chromatin states. How genome compartmentalization is regulated remains elusive. Here, comparison of mouse ground-state embryonic stem cells (ESCs) characterized by open and active chromatin, and advanced serum ESCs with a more closed and repressed genome, reveals distinct regulation of their genome organization due to differential dependency on BAZ2A/TIP5, a component of the chromatin remodeling complex NoRC. On ESC chromatin, BAZ2A interacts with SNF2H, DNA topoisomerase 2A (TOP2A) and cohesin. BAZ2A associates with chromatin subdomains within the active A compartment, which intersect through long-range contacts. We found that ground-state chromatin selectively requires BAZ2A to limit the invasion of active domains into repressive compartments. BAZ2A depletion increases chromatin accessibility at B compartments. Furthermore, BAZ2A regulates H3K27me3 genome occupancy in a TOP2A-dependent manner. Finally, ground-state ESCs require BAZ2A for growth, differentiation, and correct expression of developmental genes. Our results uncover the propensity of open chromatin domains to invade repressive domains, which is counteracted by chromatin remodeling to establish genome partitioning and preserve cell identity.
2020-10-20 | GSE112222 | GEO
Project description:Self-renewal and pluripotency in human embryonic stem cells (hESCs) depends upon the function of a remarkably small number of master transcription factors (TFs) that include OCT4, SOX2, and NANOG. Endogenous factors that regulate and maintain the expression of master TFs in hESCs remain largely unknown and/or uncharacterized. We use a genome-wide, proteomics approach to identify proteins associated with the OCT4 enhancer. We identify known OCT4 regulators, plus a subset of potential regulators including a zinc finger protein, ZNF207, that plays diverse roles during development. In hESCs, ZNF207 partners with master pluripotency TFs to govern self-renewal and pluripotency while simultaneously controlling commitment of cells towards ectoderm through direct regulation of neuronal TFs, including OTX2. The distinct roles of ZNF207 during differentiation occur via isoform switching. Thus, a distinct isoform of ZNF207 functions in hESCs at the nexus that balances pluripotency and differentiation to ectoderm.
2018-08-17 | GSE118637 | GEO
Project description:Self-renewal and pluripotency in human embryonic stem cells (hESCs) depends upon the function of a remarkably small number of master transcription factors (TFs) that include OCT4, SOX2, and NANOG. Endogenous factors that regulate and maintain the expression of master TFs in hESCs remain largely unknown and/or uncharacterized. We use a genome-wide, proteomics approach to identify proteins associated with the OCT4 enhancer. We identify known OCT4 regulators, plus a subset of potential regulators including a zinc finger protein, ZNF207, that plays diverse roles during development. In hESCs, ZNF207 partners with master pluripotency TFs to govern self-renewal and pluripotency while simultaneously controlling commitment of cells towards ectoderm through direct regulation of neuronal TFs, including OTX2. The distinct roles of ZNF207 during differentiation occur via isoform switching. Thus, a distinct isoform of ZNF207 functions in hESCs at the nexus that balances pluripotency and differentiation to ectoderm.
2018-08-17 | GSE118632 | GEO
Project description:Embryonic stem cells (ESCs) can self-renew indefinitely and have the potential to differentiate into all cell types in the adult organism. Although the developmental plasticity of ESCs is mainly controlled by transcription factors, the intrinsic regulation of this process remains elusive. Here, using whole transcriptome RNA-sequencing analysis, we identified branched-chain amino acid aminotransferase-1 (Bcat1) as highly expressed in mouse ESCs. Further, deletion of the Bcat1 gene was found to impair the pluripotency and self-renewal of mouse ESCs and made cells more inclined to differentiate toward epiblast stem cells. Conversely, overexpression of Bcat1 in mouse ESCs resulted in robust self-renewal and the repression of differentiation. Mechanistically, Bcat1 regulates the expression of RAS protein activator like 1 (Rasal1), leading to activation of Ras-Erk/MAPK signaling axis, which controls the expression of a set of core transcription factors that maintain pluripotency and self-renewal. In summary, we identified for the first time that Bcat1 is essential for mouse ESCs self-renewal and pluripotency and that this effect is mediated by the Ras pathway.
2019-01-16 | GSE125023 | GEO
Project description:Embryonic stem cell (ESC) self-renewal and differentiation are governed by a broad-ranging regulatory network. Although the transcriptional regulatory mechanisms involved have been investigated extensively, post-transcriptional regulation is still poorly understood. Here we describe a critical role of the THO complex in ESC self-renewal and differentiation. We show that THO preferentially interacts with pluripotency gene transcripts through Thoc5, and is required for self-renewal at least in part by regulating their export and expression. During differentiation, THO loses its interaction with those transcripts due to reduced Thoc5 expression, leading to decreased expression of pluripotency proteins that facilitates exit from self-renewal. THO is also important for the establishment of pluripotency, as its depletion inhibits somatic cell reprogramming and blastocyst development. Together, our data indicate that THO regulates pluripotency gene mRNA export to control ESC self-renewal and differentiation, and therefore uncover a role for this aspect of post-transcriptional regulation in stem cell fate specification. mouse J1 cells were transfected with non-targeting (NT), Thoc2, and Thoc5 siRNAs. Total RNA was isolated 96 hours after transfection.
2013-11-30 | E-GEOD-51496 | biostudies-arrayexpress