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H3K36me3 Reader NPAC/GLYR1 Recruits H3K4 Demethylase LSD2/KDM1B to Modulate Active Gene Transcription

ABSTRACT: NPAC ChIP were performed by anti-Flag and anti-HA tandem affinity purification from HeLa stably expressing Flag-HA tagged NPAC from pOZ-N vector, and enrichement on chromosome 3, 21, and 22 were determined by chip microarray analysis using Affymatrix HumanTiling 2.0 arrays

ORGANISM(S): Homo sapiens

PROVIDER: GSE160129 | GEO | 2021/10/31

REPOSITORIES: GEO

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Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation.

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Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating H3K4me2 methylation

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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.

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