Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating H3K4me2 methylation
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ABSTRACT:
PROVIDER: PRJNA128119 | ENA |
REPOSITORIES: ENA
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Project description:Dynamic histone H3K4 methylation is an important epigenetic component of transcriptional regulation. However, most of our current understanding of this histone mark is confined to regulation of transcriptional initiation. We now show that human LSD2/KDM1b/AOF1, the human homolog of LSD1, is a novel H3K4me1/2 demethylase that specifically regulates histone H3K4 methylation within intragenic regions of its target genes. Genome-wide mapping reveals that LSD2 associates predominantly with the gene bodies of actively transcribed genes, but is markedly absent from promoters. Depletion of endogenous LSD2 results in an increase of H3K4me2 as well as a decrease of H3K9me2 at LSD2 binding sites, and a consequent dysregulation of target gene transcription. Furthermore, characterization of LSD2 complex revealed that LSD2 forms active complexes with euchromatic histone methyltransferases EHMT1/2 and NSD3 as well as cellular factors involved in active transcription elongation. These data provide a possible molecular mechanism linking LSD2 to transcriptional regulation post initiation. We used microarray analysis to identify the subset of genes that are differentially expression after depletion of endogenous LSD2/KDM1b/AOF1. Retroviral shRNA targeting human LSD2 (5â-GTGGGACCACAATGAATTCTT -3â) and control shRNA was used to infect HeLa. RNA was purified 70 hours post infection and processed for Human Genome U133 Plus 2.0 Array (Affymetrix) hybridization per manufactureâs instructions. Biological duplicates were analyzed.
2010-11-01 | E-GEOD-22859 | biostudies-arrayexpress
Project description:Dynamic histone H3K4 methylation is an important epigenetic component of transcriptional regulation. However, most of our current understanding of this histone mark is confined to regulation of transcriptional initiation. We now show that human LSD2/KDM1b/AOF1, the human homolog of LSD1, is a novel H3K4me1/2 demethylase that specifically regulates histone H3K4 methylation within intragenic regions of its target genes. Genome-wide mapping reveals that LSD2 associates predominantly with the gene bodies of actively transcribed genes, but is markedly absent from promoters. Depletion of endogenous LSD2 results in an increase of H3K4me2 as well as a decrease of H3K9me2 at LSD2 binding sites, and a consequent dysregulation of target gene transcription. Furthermore, characterization of LSD2 complex revealed that LSD2 forms active complexes with euchromatic histone methyltransferases EHMT1/2 and NSD3 as well as cellular factors involved in active transcription elongation. These data provide a possible molecular mechanism linking LSD2 to transcriptional regulation post initiation. We used microarray analysis to identify the subset of genes that are differentially expression after depletion of endogenous LSD2/KDM1b/AOF1.
2010-11-01 | GSE22859 | GEO
Project description:Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating H3K4me2 methylation
| PRJNA128119 | ENA
Project description:Dynamic histone H3K4 methylation is an important epigenetic component of transcriptional regulation. However, most of our current understanding of this histone mark is confined to regulation of transcriptional initiation. We now show that human LSD2/KDM1b/AOF1, the human homolog of LSD1, is a novel H3K4me1/2 demethylase that specifically regulates histone H3K4 methylation within intragenic regions of its target genes. Genome-wide mapping reveals that LSD2 associates predominantly with the gene bodies of actively transcribed genes, but is markedly absent from promoters. Depletion of endogenous LSD2 results in an increase of H3K4me2 as well as a decrease of H3K9me2 at LSD2 binding sites, and a consequent dysregulation of target gene transcription. Furthermore, characterization of LSD2 complex revealed that LSD2 forms active complexes with euchromatic histone methyltransferases EHMT1/2 and NSD3 as well as cellular factors involved in active transcription elongation. These data provide a possible molecular mechanism linking LSD2 to transcriptional regulation post initiation.
2010-11-01 | GSE22870 | GEO
Project description:Dynamic histone H3K4 methylation is an important epigenetic component of transcriptional regulation. However, most of our current understanding of this histone mark is confined to the regulation of transcriptional initiation. We now show that human LSD2/KDM1b/AOF1, the human homolog of LSD1, is an H3K4me1/2 demethylase that specifically regulates histone H3K4 methylation within intragenic regions of its target genes. Genome-wide mapping reveals that LSD2 associates predominantly with the gene bodies of actively transcribed genes, but is markedly absent from promoters. Depletion of endogenous LSD2 results in an increase of H3K4me2 as well as a decrease of H3K9me2 at LSD2-binding sites and a consequent dysregulation of target gene transcription. Furthermore, characterization of the LSD2 complex reveals that LSD2 forms active complexes with euchromatic histone methyltransferases G9a and NSD3 as well as cellular factors involved in transcription elongation. These data provide a possible molecular mechanism linking LSD2 to transcriptional regulation after initiation.
| S-EPMC3518444 | biostudies-literature
Project description:Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating H3K4me2 methylation (Affymetrix)
| PRJNA129135 | ENA
Project description:Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation (ChIP-chip)
| PRJNA129119 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2010-11-01 | GSE22872 | GEO
Project description:Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with glioma initiating cells (GICs) implicated to be critical for tumor progression and resistance to therapy. KDM1B is involved in regulating GICs' responses to hypoxia, since over-expression of KDM1B delays the cell growth under hypoxia while knocking-down of KDM1B in GICs promotes their survival and tumorigenic abilities.
2015-12-28 | GSE73573 | GEO
Project description:DNA damage causes cancer, impairs development and accelerates aging. UV irradiation induces transcription-blocking lesions and defects in transcription-coupled nucleotide excision repair lead to developmental failure and premature aging in humans. Following DNA repair, the homeostatic processes need to be reestablished to ensure development and maintain tissue functionality. Here, we report that in C. elegans removal of the MLL/COMPASS H3K4 methyltransferase exacerbates the developmental growth retardation and accelerates aging, while depletion of the H3K4 demethylase, SPR-5, promotes developmental growth and extends lifespan amid UV-induced damage. We demonstrate that specifically the DDR-induced H3K4me2 is associated with the activation of genes regulating RNA transport, splicing, ribosome biogenesis, and protein homeostasis and regulates the recovery of protein biosynthesis that is essential for survival of UV-induced DNA damage. Our study uncovers a role of H3K4me2 in coordinating the recovery of protein biosynthesis and homeostasis that is required for developmental growth and longevity after DNA damage.
2020-10-13 | PXD015354 | Pride