Polycomb Group Protein YY1 is an Essential Regulator of Hematopoietic Stem Cell Quiescence
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ABSTRACT:
PROVIDER: PRJNA428242 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6435544.fastq.gz | Fastqsanger.gz | |||
| SRR6435545.fastq.gz | Fastqsanger.gz | |||
| SRR6435546.fastq.gz | Fastqsanger.gz | |||
| SRR6435547.fastq.gz | Fastqsanger.gz | |||
| SRR6435548.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to identify Yy1 regulated genetic network by comparing transcriptome in Yy1 deficient HSCs with wild-type HSCs. Methods: Total RNA was purified from bone marrow HSCs (Lin-Sca1+c-Kit+ CD48-CD150+and Lin-Sca1+c-Kit+CD48-CD150-) sorted from Yy1-/- versus Yy1+/+ mice using RNeasy Micro kit (Qiagen). Sequencing libraries were prepared by using Ovation RNA-Seq System V2 (NuGen) according to the manufacturer’s specifications and were sequenced by an Illumina HiSeq 2000. Sequencing reads were adapter and quality trimmed using the Skewer trimming program. Quality reads were subsequently aligned to the annotated reference genome using Subjunc aligner from subread package. qRT–PCR validation was performed using SYBR Green assays. Results: This analysis identified a small cohort of 100 significantly upregulated and 49 downregulated genes in Yy1-/- HSCs (FDR<0.05, logFC>=1). Among them, many genes involved in cell cycle were deregulated in Yy1-/- HSCs . Gene ontology analysis of the upregulated cohort revealed a significant enrichment of genes involved in cell cycle, cell division, chromosome condensation and segregation, cytoskeleton and spindle organizations. Gene Set Enrichment Analysis (GSEA) revealed cell cycle gene sets associated with pre-replication complex (RC) assembly, degradation of p27, DNA replication, G1 to S phase, and M to G1 phase transitions were significantly enriched. The RNA-seq analysis revealed that YY1-deficient HSCs had an aberrant genetic network associated with G0 to G1 phase entry.
2018-02-02 | GSE108672 | GEO
Project description:Yin yang 1 (YY1) is a ubiquitous transcription factor and mammalian polycomb group protein (PcG) with important functions to regulate embryonic development, lineage differentiation, and cell proliferation. YY1 mediates stable PcG-dependent transcriptional repression via recruitment of PcG proteins that catalyze histone modifications. Many questions remain unanswered regarding how cell- and tissue-specificity is achieved by PcG proteins. Here, we demonstrate that a conditional knockout of Yy1 in hematopoietic stem cells (HSCs) decreases long-term repopulating activity and ectopic YY1 expression expands HSCs. Although the YY1 PcG domain is required for Ig? chain rearrangement in B cells, the YY1 mutant lacking the PcG domain retained the capacity to stimulate HSC self-renewal. YY1 deficiency deregulated the genetic network governing HSC cell proliferation and impaired stem cell factor/c-Kit signaling, disrupting mechanisms conferring HSC quiescence. These results reveal a mechanism for how a ubiquitously expressed transcriptional repressor mediates lineage-specific functions to control adult hematopoiesis.
| S-EPMC6140794 | biostudies-literature
Project description:Polycomb group proteins are transcriptional repressors that control cell identity and development. In mammals, at least five different CBX proteins are believed to associate with the core Polycomb repressive complex 1 (PRC1). CBX6 and CBX7 are the most highly expressed CBX proteins in embryonic stem cells (ESCs), yet little is known about the function of CBX6 in these cells. Here we show that CBX6 is an essential regulator of ESC identity, since ablation of CBX6 function destabilizes the pluripotency network and triggers differentiation. At the molecular level, CBX6 is linked to the canonical PRC1 (cPRC1) complex; however, contrary to expectations, our results indicate that CBX6 also has a non-canonical PRC1 function. Taken together, our findings reveal that CBX6 is an essential component for ESC biology and contributes to the structural and functional complexity of the PRC1 complex.
2017-09-25 | PXD007577 | Pride
Project description:Rationale: Cardiogenesis is regulated by a complex interplay between transcription factors and chromatin-modifying enzymes. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs). Objective: To identify novel regulators of mesodermal cardiac lineage commitment. Methods and Results: We performed a bioinformatic-based transcription factor-binding site analysis on upstream promoter regions of genes that are enriched in ES cell-derived CPCs. From 32 candidate transcription factors screened, we found that YY1, a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1 kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays and in vivo chromatin immunoprecipitation (ChIP) and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with GATA4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by ES cell-based assays where we show that the over-expression of YY1 enhanced the cardiogenic differentiation ES cells into CPCs in a cell autonomous manner. Conclusion: These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes. We report the identification of putative YY1 target genes in cardiac progenitor cells (CPCs). Two samples of independently FACS-purified eGFP+ CPCs were examined against the input.
2013-06-01 | E-GEOD-35370 | biostudies-arrayexpress
Project description:YY1 is a ubiquitously expressed transcription factor that has been demonstrated to be essential for pro-B cell development. However, the role of YY1 in other B cell populations has never been investigated. It has been proposed that YY1 is a key regulator for the germinal center B cell program since the YY1 motif was present in much higher frequency in germinal center B cell signature genes than signature genes of other B cell subsets. Indeed, in accord with this prediction, we demonstrated that deletion of YY1 by Cg1-Cre completely prevented differentiation of naïve B cells into germinal center B cells and plasma cells after antigen stimulation. To determine if YY1 was also required for the differentiation of other B cell populations, we deleted YY1 with CD19-Cre and found that all peripheral B cell subsets including B1 B cells require YY1 for their differentiation. By deleting YY1 acutely with ER-Cre, we demonstrated that all B cell subsets require YY1 for their maintenance. ChIP-seq shows that YY1 predominantly binds to promoters, and pathway analysis of the genes which bind YY1 show that they are enriched in ribosomal functions, mitochondrial functions such as bioenergetics, and functions related to transcription, such as mRNA splicing, metabolism of RNA. By RNA-seq analysis of differentially expressed genes, we demonstrated that YY1 normally activates genes involved in mitochondrial bioenergetics, while it normally downregulates genes involved in transcription, mRNA splicing, NF-kB signaling pathways, AP-1 transcription factor network, chromatin remodeling, cytokine signaling pathways, cell adhesion, cell proliferation and c-Myc targets.
2016-06-20 | GSE73532 | GEO
Project description:YY1 is a ubiquitously expressed transcription factor that has been demonstrated to be essential for pro-B cell development. However, the role of YY1 in other B cell populations has never been investigated. It has been proposed that YY1 is a key regulator for the germinal center B cell program since the YY1 motif was present in much higher frequency in germinal center B cell signature genes than signature genes of other B cell subsets. Indeed, in accord with this prediction, we demonstrated that deletion of YY1 by Cg1-Cre completely prevented differentiation of naïve B cells into germinal center B cells and plasma cells after antigen stimulation. To determine if YY1 was also required for the differentiation of other B cell populations, we deleted YY1 with CD19-Cre and found that all peripheral B cell subsets including B1 B cells require YY1 for their differentiation. By deleting YY1 acutely with ER-Cre, we demonstrated that all B cell subsets require YY1 for their maintenance. ChIP-seq shows that YY1 predominantly binds to promoters, and pathway analysis of the genes which bind YY1 show that they are enriched in ribosomal functions, mitochondrial functions such as bioenergetics, and functions related to transcription, such as mRNA splicing, metabolism of RNA. By RNA-seq analysis of differentially expressed genes, we demonstrated that YY1 normally activates genes involved in mitochondrial bioenergetics, while it normally downregulates genes involved in transcription, mRNA splicing, NF-kB signaling pathways, AP-1 transcription factor network, chromatin remodeling, cytokine signaling pathways, cell adhesion, cell proliferation and c-Myc targets.
2016-06-20 | GSE73531 | GEO
Project description:Polycomb group proteins are transcriptional repressors that control cell identity and development. In mammals, at least five different CBX proteins are believed to associate with the core Polycomb repressive complex 1 (PRC1). CBX6 and CBX7 are the most highly expressed CBX proteins in embryonic stem cells (ESCs), yet little is known about the function of CBX6 in these cells. Here we show that CBX6 is an essential regulator of ESC identity, since ablation of CBX6 function destabilizes the pluripotency network and triggers differentiation. At the molecular level, CBX6 is linked to the canonical PRC1 (cPRC1) complex; however, contrary to expectations, our results indicate that CBX6 also has a non-canonical PRC1 function. Taken together, our findings reveal that CBX6 is an essential component for ESC biology and contributes to the structural and functional complexity of the PRC1 complex.
2017-09-15 | GSE98723 | GEO
Project description:Organismal homeostasis and regeneration are predicated on committed stem cells which, in tissues and organs with low turnover, reside for long periods in a reversible cell cycle arrest, defined as quiescence. Inability to exit or premature escape from quiescence, as occurring in pathological conditions and aging, is detrimental as it results in either lack of stem cell mobilization or pool depletion with consequent defective tissue homeostatis and regeneration. It is therefore unsurprising that quiescence is safeguarded by multilayered regulatory mechanisms. Here, we report that Polycomb Ezh1 confers quiescence to muscle stem cells (MuSCs) through a non-canonical function. In the absence of Ezh1, MuSCs spontaneously exit quiescence and, following repeated injuries, the stem cell pool is depleted resulting in failure to sustain appropriate muscle regeneration. Rather than regulating repressive Polycomb-dependent histone H3K27 methylation, Ezh1 actively maintains the Notch signaling pathway in MuSCs. Accordingly, selective genetic reconstitution of the Notch signaling corrects stem cell number and re-establishes quiescence of Ezh1-/- MuSCs.
2023-04-04 | GSE219232 | GEO
Project description:YY1 is a structural regulator of enhancer-promoter loops
| PRJNA388690 | ENA
Project description:Rationale: Cardiogenesis is regulated by a complex interplay between transcription factors and chromatin-modifying enzymes. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs). Objective: To identify novel regulators of mesodermal cardiac lineage commitment. Methods and Results: We performed a bioinformatic-based transcription factor-binding site analysis on upstream promoter regions of genes that are enriched in ES cell-derived CPCs. From 32 candidate transcription factors screened, we found that YY1, a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1 kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays and in vivo chromatin immunoprecipitation (ChIP) and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with GATA4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by ES cell-based assays where we show that the over-expression of YY1 enhanced the cardiogenic differentiation ES cells into CPCs in a cell autonomous manner. Conclusion: These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes.
2013-06-01 | GSE35370 | GEO