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Publication : Setd5 is essential for mammalian development and the co-transcriptional regulation of histone acetylation.

First Author  Osipovich AB Year  2016
Journal  Development Volume  143
Issue  24 Pages  4595-4607
PubMed ID  27864380 Mgi Jnum  J:237500
Mgi Id  MGI:5812827 Doi  10.1242/dev.141465
Citation  Osipovich AB, et al. (2016) Setd5 is essential for mammalian development and the co-transcriptional regulation of histone acetylation. Development 143(24):4595-4607
abstractText  SET domain-containing proteins play a vital role in regulating gene expression during development through modifications in chromatin structure. Here we show that SET domain-containing 5 (Setd5) is divergently transcribed with Gt(ROSA26)Sor, is necessary for mammalian development, and interacts with the PAF1 co-transcriptional complex and other proteins. Setd5-deficient mouse embryos exhibit severe defects in neural tube formation, somitogenesis and cardiac development, have aberrant vasculogenesis in embryos, yolk sacs and placentas, and die between embryonic day 10.5 and 11.5. Setd5-deficient embryonic stem cells have impaired cellular proliferation, increased apoptosis, defective cell cycle progression, a diminished ability to differentiate into cardiomyocytes and greatly perturbed gene expression. SETD5 co-immunoprecipitates with multiple components of the PAF1 and histone deacetylase-containing NCoR complexes and is not solely required for major histone lysine methylation marks. In the absence of Setd5, histone acetylation is increased at transcription start sites and near downstream regions. These findings suggest that SETD5 functions in a manner similar to yeast Set3p and Drosophila UpSET, and that it is essential for regulating histone acetylation during gene transcription.
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