Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LSD1/KDM1 regulates the balance between self-renewal and differentiation in human embryonic stem cells.

ABSTRACT: Embryonic stem (ES) cells have the ability to differentiate into all the cell types of the adult organism. This unusual property has been proposed to emanate from a particular chromatin environment that simultaneously contains both H3K4 and H3K27 trimethylation marks at the regulatory regions of the developmental genes, which are thus poised for activation during differentiation following resolution of these “bivalent domains.” Our work identifies Lysine Specific Demethylase 1 (LSD1/AOF2/KDM1A) as a key histone modifier in the maintenance of pluripotency. We show that the knock-down of LSD1 causes the differentiation of human ES cells and the induction of key endo- and mesodermal genes marked with bivalent domains. This induction correlates with an increase in the levels of H3K4 methylation at the regulatory regions of these genes. ChIP on chip analysis reveals that in human ES cells LSD1 preferentially occupies the promoters of a subset of developmental genes that contain bivalent domains that are also occupied by OCT4 and NANOG. We conclude that LSD1 contributes to maintain a subset of developmental genes in human ES in a silenced state by maintaining the critical balance between H3K4 and H3K27 methylation at the regulatory regions of these genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE24844 | GEO | 2011/05/27

SECONDARY ACCESSION(S): PRJNA132061

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation [RNA-Seq]

Project description:Pluripotency of embryonic stem (ES) cells is controlled in part by chromatin-modifying factors that regulate histone H3 lysine 4 (H3K4) methylation. However, it remains unclear how H3K4 demethylation contributes to ES cell function. Here, we show that KDM5B, which demethylates lysine 4 of histone H3, co-localizes with H3K4me3 near promoters and enhancers of active genes in ES cells; its depletion leads to spreading of H3K4 methylation into gene bodies and enhancer shores, indicating that KDM5B functions to focus H3K4 methylation at promoters and enhancers. Spreading of H3K4 methylation to gene bodies and enhancer shores is linked to defects in gene expression programs and enhancer activity, respectively, during self-renewal and differentiation of KDM5B-depleted ES cells. KDM5B critically regulates H3K4 methylation at bivalent genes during differentiation in the absence of LIF or Oct4. We also show that KDM5B and LSD1, another H3K4 demethylase, co-regulate H3K4 methylation at active promoters but they retain distinct roles in demethylating gene body regions and bivalent genes. Our results provide global and functional insight into the role of KDM5B in regulating H3K4 methylation marks near promoters, gene bodies, and enhancers in ES cells and during differentiation. RNA-Seq of murine shLuc and shKdm5b ES cells differentiated for 72h in the absence of LIF.

2014-01-27 | E-GEOD-53090 | biostudies-arrayexpress

KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation [ChIP-Seq]

Project description:Pluripotency of embryonic stem (ES) cells is controlled in part by chromatin-modifying factors that regulate histone H3 lysine 4 (H3K4) methylation. However, it remains unclear how H3K4 demethylation contributes to ES cell function. Here, we show that KDM5B, which demethylates lysine 4 of histone H3, co-localizes with H3K4me3 near promoters and enhancers of active genes in ES cells; its depletion leads to spreading of H3K4 methylation into gene bodies and enhancer shores, indicating that KDM5B functions to focus H3K4 methylation at promoters and enhancers. Spreading of H3K4 methylation to gene bodies and enhancer shores is linked to defects in gene expression programs and enhancer activity, respectively, during self-renewal and differentiation of KDM5B-depleted ES cells. KDM5B critically regulates H3K4 methylation at bivalent genes during differentiation in the absence of LIF or Oct4. We also show that KDM5B and LSD1, another H3K4 demethylase, co-regulate H3K4 methylation at active promoters but they retain distinct roles in demethylating gene body regions and bivalent genes. Our results provide global and functional insight into the role of KDM5B in regulating H3K4 methylation marks near promoters, gene bodies, and enhancers in ES cells and during differentiation. ChIP-Seq for KDM5B, H3K4 methylation and H3K27ac in murine shLuc, shKdm5b, shLuc-LSD1i, shKdm5b-LSD1i ES cells, and during differentiation of shLuc and shKdm5b ES cells for 2 days, 3 days, and 4 days without LIF.

2014-01-27 | E-GEOD-53087 | biostudies-arrayexpress

KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation [RNA-Seq]

2014-01-27 | GSE53090 | GEO

KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation [ChIP-Seq]

2014-01-27 | GSE53087 | GEO

Mammalian Dpy-30 regulates genomic H3K4 methylation and is essential for ES cell fate specification

Project description:H3K4 methylation is associated with active genes and, along with H3K27 methylation, is part of a bivalent chromatin mark that typifies poised developmental genes in ESCs. However, its functional roles in ESC maintenance and differentiation are not established. Here we show that mammalian Dpy-30, a core subunit of SET1/MLL complexes, biochemically modulates H3K4 methylation in vitro, and directly regulates chromosomal H3K4me3 throughout the mammalian genome. Depletion of Dpy-30 does not affect ESC self-renewal, but significantly alters the differentiation potential of ESCs, particularly along the neural lineage. The differentiation defect is accompanied by defects in gene induction and H3K4 methylation at key developmental loci. Our results provide strong experimental evidence for the hypothesis that H3K4 methylation is an essential functional component of the bivalent mark during activation of developmental genes in ESCs. Total RNAs from control or knockdown cells before and after RA-mediated differentiation were subjected to Illumina microarray analyses. ChIP-enriched DNA from mouse ES cells was analyzed by Solexa sequencing.

2011-02-01 | E-GEOD-26136 | biostudies-arrayexpress

Genome wide analysis of bivalent domains in two HUES cell lines

Project description:Human embryonic stem (HUES) cells are derived from early individual embryos with unique genetic properties. However, how their epigenetic status might affect their potential to differentiate toward specific lineages remains a puzzling question. Using ChIP-on-chip, the status of bivalent domains on gene promoters (i.e. H3K4 and H3K27 trimethylation) was monitored for both undifferentiated and BMP2 induced cardiac committed cells. A marked difference in the epigenetic profile of HUES cell lines was observed and this was correlated to the pattern of gene expression induced by BMP2 as well as to their potential to generate cardiac progenitors and differentiated myocytes. Thus, the epigenetic H3trimeK4 and H3trimeK27 prints generating bivalent domains on promoters, could be used to predict a preference in their differentiation toward a specific lineage. Using ChIP-on-chip, the status of bivalent domains on gene promoters (i.e. H3K4 and H3K27 trimethylation) was monitored for both undifferentiated and BMP2 induced cardiac committed cells.

2014-10-06 | E-GEOD-59328 | biostudies-arrayexpress

Mammalian Dpy-30 regulates genomic H3K4 methylation and is essential for ES cell fate specification

2011-02-01 | GSE26136 | GEO

H4K20me3 co-localizes with activating histone modifications at transcriptionally dynamic regions in embryonic stem cells

Project description:Bivalent chromatin domains consisting of the activating histone 3 lysine 4 trimethylation (H3K4me3) and repressive histone 3 lysine 27 trimethylation (H3K27me3) histone modifications are enriched at developmental genes that are repressed in embryonic stem cells but active during differentiation. However, it is unknown whether another repressive histone modification, histone 4 lysine 20 trimethylation (H4K20me3), co-localizes with activating histone marks in ES cells. Here, we describe the previously uncharacterized coupling of the repressive H4K20me3 heterochromatin mark with the activating histone modifications H3K4me3 and histone 3 lysine 36 trimethylation (H3K36me3), and transcriptional machinery (RNA polymerase II; RNAPII), in ES cells. These newly described bivalent domains consisting of H3K4me3/H4K20me3 are predominantly located in intergenic regions and near transcriptional start sites of active genes, while H3K36me3/H4K20me3 are located in intergenic regions and within gene body regions of active genes. Global sequential ChIP, also termed reChIP-Seq, confirmed the simultaneous presence of H3K4me3 and H4K20me3 at the same genomic regions in ES cells. Genes containing H3K4me3/H4K20me3 exhibit decreased RNAPII pausing and are poised for deactivation of RNAPII binding during differentiation relative to H3K4me3 marked genes. An evaluation of transcription factor (TF) binding motif enrichment revealed that DNA sequence may play a role in shaping the landscape of these novel bivalent domains. Moreover, H3K4me3/H4K20me3 and H3K36me3/H4K20me3 bound regions are enriched with repetitive LINE and LTR elements.

2018-06-18 | GSE115907 | GEO

Effect of LSD1 knockdown on histone H3K4 methylation in HEL human erythroleukemia cell line.

Project description:To understand the role of LSD1 in regulating histone H3K4 methylation status, ChIP-seq analyse of mono- and di-methylated H3K4 in LSD1-KD HEL cells were performed. The analyses revealed demethylation of H3K4me1 and H3K4me2 by LSD1 at regulatory regions including CEBPA gene enhancer.

2021-05-04 | GSE145399 | GEO

H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions

Project description:The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure. We mapped H2A.Z genome-wide in mammalian ES cells and neural progenitors. H2A.Z is deposited promiscuously at promoters and enhancers, and correlates strongly with H3K4 methylation. Accordingly, H2A.Z is present at poised promoters with bivalent chromatin and at active promoters with H3K4 methylation, but is absent from stably repressed promoters that are specifically enriched for H3K27 trimethylation. We also characterized post-translational modification states of H2A.Z, including a novel species dually-modified by ubiquitination and acetylation that is enriched at bivalent chromatin. Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that post-translational modifications may reconcile its contrasting locations and roles. Examination of histone variant, histone modifications and transcription machinery in 3 cell types

2012-07-19 | E-GEOD-39237 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data