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Human Molecular Genetics Advance Access published online on January 7, 2005

Human Molecular Genetics, doi:10.1093/hmg/ddi048
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Human Molecular Genetics © Oxford University Press 2005; all rights reserved

Article

CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2L

Graham S. Banting 1, Orr Barak 2, Tanya M. Ames 3, Amanda C. Burnham 3, Melanie D. Kardel 3, Neil S. Cooch 2, Courtney E. Davidson 3, Roseline Godbout 4, Heather E. McDermid 3*, and Ramin Shiekhattar 2

1 Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9 Canada; Department of Medical Genetics, University of Alberta, Edmonton, AB, T6G 2H7, Canada
2 The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA
3 Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9 Canada
4 Cross Cancer Institute, Edmonton, AB, T6G 1Z2, Canada

* To whom correspondence should be addressed.
Heather E. McDermid, E-mail: hmcdermi{at}ualberta.ca


   Abstract

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 is comprised of 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.


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