Ontology highlight
ABSTRACT:
PROVIDER: PRJNA138041 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE27714: Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (expression) GSE27841: Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (ChIP-seq) Refer to individual Series
2012-01-03 | E-GEOD-27844 | biostudies-arrayexpress
Project description:Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (expression)
| PRJNA141807 | ENA
Project description:Enhancer Decommissioning by LSD1 During Embryonic Stem Cell Differentiation (ChIP-seq)
| PRJNA141891 | ENA
Project description:Transcription factors and chromatin modifiers play important roles in programming and reprogramming of cellular states during development. Much is known about the role of these regulators in gene activation, but relatively little is known about the critical process of enhancer silencing during differentiation. Here we show that the H3K4/K9 histone demethylase LSD1 plays an essential role in decommissioning enhancers during differentiation of embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes critical for control of ESC state. However, LSD1 is not essential for maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to fully differentiate and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At enhancers, LSD1 is a component of the NuRD complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program upon differentiation, which is essential for complete shutdown of the ESC gene expression program and the transition to new cell states. This is the ChIP-seq part of the study.
2012-01-03 | E-GEOD-27841 | biostudies-arrayexpress
Project description:Transcription factors and chromatin modifiers play important roles in programming and reprogramming of cellular states during development. Much is known about the role of these regulators in gene activation, but relatively little is known about the critical process of enhancer silencing during differentiation. Here we show that the H3K4/K9 histone demethylase LSD1 plays an essential role in decommissioning enhancers during differentiation of embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes critical for control of ESC state. However, LSD1 is not essential for maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to fully differentiate and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At enhancers, LSD1 is a component of the NuRD complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program upon differentiation, which is essential for complete shutdown of the ESC gene expression program and the transition to new cell states. This represents the expression part of the study.
2012-01-03 | E-GEOD-27714 | biostudies-arrayexpress
Project description:Transcription factors and chromatin modifiers play important roles in programming and reprogramming of cellular states during development. Much is known about the role of these regulators in gene activation, but relatively little is known about the critical process of enhancer silencing during differentiation. Here we show that the H3K4/K9 histone demethylase LSD1 plays an essential role in decommissioning enhancers during differentiation of embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes critical for control of ESC state. However, LSD1 is not essential for maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to fully differentiate and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At enhancers, LSD1 is a component of the NuRD complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program upon differentiation, which is essential for complete shutdown of the ESC gene expression program and the transition to new cell states.
2012-01-03 | GSE27841 | GEO
Project description:Transcription factors and chromatin modifiers play important roles in programming and reprogramming of cellular states during development. Much is known about the role of these regulators in gene activation, but relatively little is known about the critical process of enhancer silencing during differentiation. Here we show that the H3K4/K9 histone demethylase LSD1 plays an essential role in decommissioning enhancers during differentiation of embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes critical for control of ESC state. However, LSD1 is not essential for maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to fully differentiate and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At enhancers, LSD1 is a component of the NuRD complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program upon differentiation, which is essential for complete shutdown of the ESC gene expression program and the transition to new cell states.
2012-01-03 | GSE27714 | GEO
Project description:Enhancer reactivation and pluripotency gene (PpG) expression could induce stemness and enhance tumorigenicity in cancer stem cells. Silencing of PpG enhancers (PpGe) during embryonic stem cell differentiation involves Lsd1–mediated H3K4me1 demethylation followed by DNA methylation. Here, we observed a widespread retention of H3K4me1 and DNA hypomethylation at PpGe associated with a partial repression of PpGs in F9 embryonal carcinoma cells (ECCs) post-differentiation. The absence of H3K4me1 demethylation could not be rescued by Lsd1 overexpression. Based on the observation that H3K4me1 demethylation is accompanied by strong Oct4 repression in P19 ECCs, we tested if Lsd1-Oct4 interaction affects Lsd1 catalytic activity. Our data show a dose-dependent inhibition of Lsd1 by Oct4 in vitro and retention of H3K4me1 at PpGe post-differentiation in Oct4 overexpressing P19 ECCs. These data suggest that Lsd1-Oct4 interaction in cancer stem cells may establish a primed enhancer state that is susceptible to reactivation leading to aberrant PpG expression.
2020-06-29 | GSE135225 | GEO
Project description:Here we describe that lysine-specific demethylase 1 (Lsd1/KDM1a), which demethylates histone H3 on LysM-bM-^@M-^I4 or LysM-bM-^@M-^I9 (H3K4/K9), is an indispensible epigenetic governor of hematopoietic differentiation. Integrative genomic analysis in primary hematopoietic cells, combining global occupancy of Lsd1, genome-wide analysis of its histone substrates H3K4 mono- and di-methylation and gene expression profiling, reveals that Lsd1 represses hematopoietic stem and progenitor cell (HSPC) gene expression programs during hematopoietic differentiation. We found that Lsd1 function was not restricted to transcription start sites, but is also critical at enhancers. Loss of Lsd1 at these sites was associated with increased H3K4me1 and H3K4me2 methylation levels on HSPC genes and their derepression. Failure to fully silence HSPC genes compromised differentiation of hematopoietic stem cells and mature blood cell lineages. Our data indicate that Lsd1-mediated concurrent repression of enhancer and promoter activity of stem and progenitor cell genes is a pivotal epigenetic mechanism required for proper hematopoietic maturation. To identify direct target genes of Lsd1 in myeloid cells we mapped global occupancy of Lsd1 in 32D granuolocytic progenitor cells and compared H3K4me1/me2/me3 and H3K27ac histone modifications in Lsd1fl/fl (wild type) vs. Lsd1fl/f Mx1Cre (knockout) Gr1dim Mac1 granuolocytic progenitor cells.
2013-06-25 | E-GEOD-40440 | biostudies-arrayexpress
Project description:Lysine-specific demethylase 1 (LSD1) catalyzes the demethylation at H3K4 and H3K9 and is well- known for its role in decommissioning enhancers during mouse embryonic stem cell (ESC) differentiation. However, its role at gene promoters remains poorly understood in ESCs despite their widespread presence at these sites. Here, we report that LSD1 promotes RNA Polymerase II (RNAPII) pausing, a rate-limiting step in transcription regulation, in ESCs. We found that the knockdown of LSD1 preferentially affects genes with higher RNAPII pausing than those with lower pausing. We show that LSD1 knockdown leads to the global reduction in RNAPII pausing and most significantly on the genes bound by LSD1. Next, we demonstrate that the co-localization of LSD1 and MYC, a factor known to regulate pause-release, is associated with the enrichment of other RNAPII pausing factors. Finally, we found that genes co-occupied by LSD1 and MYC are significantly enriched for housekeeping genes that are involved in metabolic processes and depleted of transcription factors compared to those bound only by LSD1. Our integrative analysis reveals a pleiotropic role of LSD1 in promoting RNAPII pausing and in regulating housekeeping programs besides its known role in regulating cell identity programs.
2022-08-16 | GSE173089 | GEO