CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2L.
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.
Banting
Graham S
GS
Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
Barak
Orr
O
Ames
Tanya M
TM
Burnham
Amanda C
AC
Kardel
Melanie D
MD
Cooch
Neil S
NS
Davidson
Courtney E
CE
Godbout
Roseline
R
McDermid
Heather E
HE
Shiekhattar
Ramin
R
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism; D002843:Chromatin; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009436:Neural Tube Defects; D009707:Nucleosomes / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C501837:CECR2 protein, mouse; D002843:Chromatin; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009707:Nucleosomes; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases