Genomics

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The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3 [ChIP-Seq]


ABSTRACT: Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb targets genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants. Genome-wide analysis demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 in early Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators in knockouts. Taken together, these results suggest that Jarid1b contributes to mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications. * Lack of Jarid1b leads to major neonatal lethality and defects in neural systems * Jarid1b mutants display homeotic skeletal transformations * H3K4me3 is increased at inactive transcriptional regulators in Jarid1b-/- embryos * Chromatin changes are accompanied by elevated levels of key neural transcription factors Determining H3K4me3 and H3K27me3 in early (E8.5) mouse embryos

ORGANISM(S): Mus musculus  

SUBMITTER: Mareike Albert   Sandra U Schmitz  Sandra Ursula Schmitz 

PROVIDER: E-GEOD-41172 | ArrayExpress | 2013-04-26

SECONDARY ACCESSION(S): SRP015906GSE41172PRJNA176031

REPOSITORIES: GEO, ArrayExpress, ENA

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The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3.

Albert Mareike M   Schmitz Sandra U SU   Kooistra Susanne M SM   Malatesta Martina M   Morales Torres Cristina C   Rekling Jens C JC   Johansen Jens V JV   Abarrategui Iratxe I   Helin Kristian K  

PLoS genetics 20130418 4


Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cr  ...[more]

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