Jarid1b targets genes regulating development and is involved in neural differentiation

TY - JOUR

T1 - Jarid1b targets genes regulating development and is involved in neural differentiation

AU - Schmitz, Sandra U

AU - Albert, Mareike

AU - Malatesta, Martina

AU - Morey Ramonell, Lluis

AU - Johansen, Jens V

AU - Bak, Mads

AU - Tommerup, Niels

AU - Abarrategui Garcia, Iratxe

AU - Helin, Kristian

PY - 2011/11/16

Y1 - 2011/11/16

N2 - H3K4 methylation is associated with active transcription and in combination with H3K27me3 thought to keep genes regulating development in a poised state. The contribution of enzymes regulating trimethylation of lysine 4 at histone 3 (H3K4me3) levels to embryonic stem cell (ESC) self-renewal and differentiation is just starting to emerge. Here, we show that the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for ESC self-renewal, but essential for ESC differentiation along the neural lineage. By genome-wide location analysis, we demonstrate that Jarid1b localizes predominantly to transcription start sites of genes encoding developmental regulators, of which more than half are also bound by Polycomb group proteins. Virtually all Jarid1b target genes are associated with H3K4me3 and depletion of Jarid1b in ESCs leads to a global increase of H3K4me3 levels. During neural differentiation, Jarid1b-depleted ESCs fail to efficiently silence lineage-inappropriate genes, specifically stem and germ cell genes. Our results delineate an essential role for Jarid1b-mediated transcriptional control during ESC differentiation.

AB - H3K4 methylation is associated with active transcription and in combination with H3K27me3 thought to keep genes regulating development in a poised state. The contribution of enzymes regulating trimethylation of lysine 4 at histone 3 (H3K4me3) levels to embryonic stem cell (ESC) self-renewal and differentiation is just starting to emerge. Here, we show that the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for ESC self-renewal, but essential for ESC differentiation along the neural lineage. By genome-wide location analysis, we demonstrate that Jarid1b localizes predominantly to transcription start sites of genes encoding developmental regulators, of which more than half are also bound by Polycomb group proteins. Virtually all Jarid1b target genes are associated with H3K4me3 and depletion of Jarid1b in ESCs leads to a global increase of H3K4me3 levels. During neural differentiation, Jarid1b-depleted ESCs fail to efficiently silence lineage-inappropriate genes, specifically stem and germ cell genes. Our results delineate an essential role for Jarid1b-mediated transcriptional control during ESC differentiation.

KW - Animals

KW - Antibodies, Monoclonal

KW - Cell Line

KW - Central Nervous System

KW - DNA-Binding Proteins

KW - Embryonic Stem Cells

KW - Gene Expression Profiling

KW - Gene Knockout Techniques

KW - Histones

KW - Jumonji Domain-Containing Histone Demethylases

KW - Methylation

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Neurogenesis

KW - Neurons

KW - Promoter Regions, Genetic

KW - RNA Interference

KW - RNA, Small Interfering

KW - Repressor Proteins

KW - Transcription, Genetic

U2 - 10.1038/emboj.2011.383

DO - 10.1038/emboj.2011.383

M3 - Journal article

C2 - 22020125

SN - 0261-4189

VL - 30

SP - 4586

EP - 4600

JO - E M B O Journal

JF - E M B O Journal

IS - 22

ER -