Article

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

Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
Human Molecular Genetics (Impact Factor: 6.68). 03/2005; 14(4):513-24. DOI: 10.1093/hmg/ddi048
Source: PubMed

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 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.

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    • "Other studies highlight a more global role for ISWI in chromatin compaction (Corona et al., 2007; Li et al., 2010). The Snf2l protein is part of two different complexes, CERF (Banting et al., 2005) and NURF (Barak et al., 2003), but which one regulates Foxg1 expression is unclear. The NURF complex is largely considered an activator of gene expression, whereas the function of the CERF complex remains unknown (Lazzaro et al., 2006; Wysocka et al., 2006). "
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    • "During Neurulation Cecr2 Is Expressed in Both the Neural Epithelium and Head Mesenchyme To better understand the role of Cecr2 during neurulation, we examined its expression during this time using the LacZ fusion protein of the Cecr2 Gt45Bic mutation. Xgal staining at 13.5 days post coitus (dpc) previously showed that Cecr2 is expressed in the nervous system (brain, spinal cord, spinal ganglia , and forming retina), as well as the nasal epithelium, lens, limb, and intercostal mesenchyme (Banting et al., 2005). Whole-mount embryos at 9.5 dpc showed Xgal staining along the closed neural tube. "
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    • "Mice harboring mutations in other Swi/Snf type complexes, including Brg1 (Bultman et al., 2000),. Srg3, and CECR2 (Banting et al., 2005), also exhibit NTDs, indicating that multiple ATP-dependent chromatin remodeling complexes are involved in neural development. Specific HATs and their binding proteins are also essential for this process. "
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