Genomics

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299

X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner [ChIP-Seq data]


ABSTRACT: Embryogenesis requires the timely and coordinated activation of developmental regulators. It has been suggested that the recently discovered class of histone demethylases (UTX and JMJD3) that specifically target the repressive H3K27me3 modification play an important role in the activation of “bivalent” genes in response to specific developmental cues. To determine the requirements for UTX in pluripotency and development, we have generated Utx null ES cells and mutant mice. The loss of UTX had a profound effect during embryogenesis. Utx null embryos had reduced somite counts, neural tube closure defects and heart malformation which presented between E9.5 and E13.5. Unexpectedly, homozygous mutant female embryos were more severely affected than hemizygous mutant male embryos. In fact, we observed the survival of a subset of UTX-deficient males which were smaller in size and had reduced life-span. Interestingly, these animals were fertile with normal spermatogenesis. Consistent with a mid-gestation lethality, UTX null male and female ES cells gave rise to all three germ layers in teratoma assays although sex-specific differences could be observed in the activation of developmental regulators in embryoid body assays. Lastly, ChIP-seq analysis revealed an increase in H3K27me3 in Utx null male ES cells. In summary, our data demonstrate sex-specific requirements for this X-linked gene while suggesting a role for UTY during development. Examination of H3K27me3 and H3K4me3 in UtxKO ES cells (V6.5 background) vs UtxFlx (V6.5 background) ES cells grown in LIF containing ES cell media or treated with retinoic acid without LIF.

ORGANISM(S): Mus musculus  

SUBMITTER: Rudolf Jaenisch   Albert W Cheng  Grant Welstead 

PROVIDER: E-GEOD-39472 | ArrayExpress | 2012-08-01

SECONDARY ACCESSION(S): GSE39472SRP014463PRJNA170980

REPOSITORIES: GEO, ArrayExpress, ENA

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X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner.

Welstead G Grant GG   Creyghton Menno P MP   Bilodeau Steve S   Cheng Albert W AW   Markoulaki Styliani S   Young Richard A RA   Jaenisch Rudolf R  

Proceedings of the National Academy of Sciences of the United States of America 20120723 32


Embryogenesis requires the timely and coordinated activation of developmental regulators. It has been suggested that the recently discovered class of histone demethylases (UTX and JMJD3) that specifically target the repressive H3K27me3 modification play an important role in the activation of "bivalent" genes in response to specific developmental cues. To determine the requirements for UTX in pluripotency and development, we have generated Utx-null ES cells and mutant mice. The loss of UTX had a  ...[more]

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