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Distinct function of 2 chromatin remodeling complexes that share a common subunit, Williams syndrome transcription factor (WSTF)
- Source :
- Proceedings of the National Academy of Sciences of the United States. June 9, 2009, Vol. 106 Issue 23, p9280, 6 p.
- Publication Year :
- 2009
-
Abstract
- A number of nuclear complexes modify chromatin structure and operate as functional units. However, the in vivo role of each component within the complexes is not known. ATP-dependent chromatin remodeling complexes form several types of protein complexes, which reorganize chromatin structure cooperatively with histone modifiers. Williams syndrome transcription factor (WSTF) was biochemically identified as a major subunit, along with 2 distinct complexes: WlNAC, a SWI/SNF-type complex, and WICH, an ISWI-type complex. Here, [WSTF.sup.-/-] mice were generated to investigate its function in chromatin remodeling in vivo. Loss of WSTF expression resulted in neonatal lethality, and all [WSTF.sup.-/-] neonates and [approximately equal to] 10% of [WSTF.sup.+/-] neonates suffered cardiovascular abnormalities resembling those found in autosomal-dominant Williams syndrome patients. Developmental analysis of [WSTF.sup.-/-] embryos revealed that Gja5 gene regulation is aberrant from E9.5, conceivably because of inappropriate chromatin reorganization around the promoter regions where essential cardiac transcription factors are recruited. In vitro analysis in [WSTF.sup.-/-] mouse embryonic fibroblast (MEF) cells also showed impaired transactivation functions of cardiac transcription activators on the Gja5 promoter, but the effects were reversed by overexpression of WiNAC components. Likewise in [WSTF.sup.-/-] MEF cells, recruitment of Snf2h, an ISWI ATPase, to PCNA and cell survival after DNA damage were both defective, but were ameliorated by overexpression of WlCH components. Thus, the present study provides evidence that WSTF is shared and is a functionally indispensable subunit of the WICH complex for DNA repair and the WINAC complex for transcriptional control. WICH | WINAC | heart development | SWI/SNF | ISWI
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 106
- Issue :
- 23
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.202487250