Human Molecular Genetics Advance Access originally published online on January 7, 2005
Human Molecular Genetics 2005 14(4):513-524; doi:10.1093/hmg/ddi048
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Human Molecular Genetics, Vol. 14, No. 4 © Oxford University Press 2005; all rights reserved
CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2L
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1Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada, 2The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA and 3Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada
Received September 18, 2004; Revised December 15, 2004; Accepted December 21, 2004
Chromatin remodeling complexes play critical roles in development. Here we describe a transcription factor, CECR2, which is involved in neurulation and chromatin remodeling. CECR2 shows complex alternative splicing, but all variants contain DDT and bromodomain motifs. A mutant mouse line was generated from an embryonic stem cell line containing a genetrap within Cecr2. Reporter gene expression demonstrated Cecr2 expression to be predominantly neural in the embryo. Mice homozygous for the Cecr2 genetrap-induced mutation show a high penetrance of the neural tube defect exencephaly, the human equivalent of anencephaly, in a strain-dependent fashion. Biochemical isolation of CECR2 revealed the presence of this protein as a component of a novel heterodimeric complex termed CECR2-containing remodeling factor (CERF). CERF comprises CECR2 and the ATP-dependent chromatin remodeler SNF2L, a mammalian ISWI ortholog expressed predominantly in the central nervous system. CERF is capable of remodeling chromatin in vitro and displays an ATP hydrolyzing activity that is stimulated by nucleosomes. Together, these data identify a novel chromatin remodeling complex with a critical role in neurulation.
* To whom correspondence should be addressed. Tel: +1 7804925377; Fax: +1 7804929234; Email: hmcdermi{at}ualberta.ca
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