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

BACKGROUND: 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. RESULTS: Here, we show that KDM5B, which demethylates l...

Full description

Saved in:
Bibliographic Details
Published in:Genome biology 2014-02, Vol.15 (2), p.R32-R32, Article R32
Main Authors: Kidder, Benjamin L, Hu, Gangqing, Zhao, Keji
Format: Article
Language:English
Subjects:
Cell Differentiation - genetics
Cell Proliferation - genetics
DNA Methylation - genetics
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Enhancer Elements, Genetic
gene expression
Gene Expression Regulation
Gene Knockdown Techniques
genes
Histone-Lysine N-Methyltransferase - genetics
Histones - metabolism
Humans
Jumonji Domain-Containing Histone Demethylases - genetics
methylation
Nuclear Proteins - genetics
Promoter Regions, Genetic
Repressor Proteins - genetics
stem cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
ISSN:1465-6906
1474-760X
1465-6914
1474-760X
DOI:10.1186/gb-2014-15-2-r32