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Publication : Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.

First Author  Verzi MP Year  2013
Journal  Mol Cell Biol Volume  33
Issue  2 Pages  281-92
PubMed ID  23129810 Mgi Jnum  J:192828
Mgi Id  MGI:5466628 Doi  10.1128/MCB.01185-12
Citation  Verzi MP, et al. (2013) Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding. Mol Cell Biol 33(2):281-92
abstractText  Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulate cell-specific chromatin and if such abilities might underlie lineage determination and maintenance. One prevailing view is that several transcription factors enable chromatin access in combination. The homeodomain protein CDX2 specifies the embryonic intestinal epithelium, through unknown mechanisms, and partners with transcription factors such as HNF4A in the adult intestine. We examined enhancer chromatin and gene expression following Cdx2 or Hnf4a excision in mouse intestines. HNF4A loss did not affect CDX2 binding or chromatin, whereas CDX2 depletion modified chromatin significantly at CDX2-bound enhancers, disrupted HNF4A occupancy, and abrogated expression of neighboring genes. Thus, CDX2 maintains transcription-permissive chromatin, illustrating a powerful and dominant effect on enhancer configuration in an adult tissue. Similar, hierarchical control of cell-specific chromatin states is probably a general property of master transcription factors.
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