Transcriptomics,Genomics

Dataset Information

423

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


ABSTRACT: 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.

ORGANISM(S): Mus musculus  

SUBMITTER: Hao Jiang   R G Roeder  H Jiang 

PROVIDER: E-GEOD-26136 | ArrayExpress | 2011-02-01

SECONDARY ACCESSION(S): GSE26136SRP006206PRJNA135385

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Role for Dpy-30 in ES cell-fate specification by regulation of H3K4 methylation within bivalent domains.

Jiang Hao H   Shukla Abhijit A   Wang Xiaoling X   Chen Wei-yi WY   Bernstein Bradley E BE   Roeder Robert G RG  

Cell 20110201 4


Histone 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 embryonic stem cells (ESCs). However, its functional roles in ESC maintenance and differentiation are not established. Here we show that mammalian Dpy-30, a core subunit of the SET1/MLL histone methyltransferase complexes, modulates H3K4 methylation in vitro, and directly regulates chromosomal H3K4 trimethylation (H3K4me3) th  ...[more]

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