Baf60c is essential for function of BAF chromatin remodelling complexes in heart development.

Abstract:

:Tissue-specific transcription factors regulate several important aspects of embryonic development. They must function in the context of DNA assembled into the higher-order structure of chromatin. Enzymatic complexes such as the Swi/Snf-like BAF complexes remodel chromatin to allow the transcriptional machinery access to gene regulatory elements. Here we show that Smarcd3, encoding Baf60c, a subunit of the BAF complexes, is expressed specifically in the heart and somites in the early mouse embryo. Smarcd3 silencing by RNA interference in mouse embryos derived from embryonic stem cells causes defects in heart morphogenesis that reflect impaired expansion of the anterior/secondary heart field, and also results in abnormal cardiac and skeletal muscle differentiation. An intermediate reduction in Smarcd3 expression leads to defects in outflow tract remodelling reminiscent of human congenital heart defects. Baf60c overexpressed in cell culture can mediate interactions between cardiac transcription factors and the BAF complex ATPase Brg1, thereby potentiating the activation of target genes. These results reveal tissue-specific and dose-dependent roles for Baf60c in recruiting BAF chromatin remodelling complexes to heart-specific enhancers, providing a novel mechanism to ensure transcriptional regulation during organogenesis.

journal_name

Nature

journal_title

Nature

authors

Lickert H,Takeuchi JK,Von Both I,Walls JR,McAuliffe F,Adamson SL,Henkelman RM,Wrana JL,Rossant J,Bruneau BG

doi

10.1038/nature03071

keywords:

subject

Has Abstract

pub_date

2004-11-04 00:00:00

pages

107-12

issue

7013

eissn

0028-0836

issn

1476-4687

pii

nature03071

journal_volume

432

pub_type

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