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Cdx2 transcription factor binding in intestinal villus and gene expression profiling in Cdx mutant mice


ABSTRACT: We conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was accelerated in mice lacking both Cdx2 and its homolog Cdx1, with exaggeration of defects in crypt cell replication and enterocyte differentiation. Cdx2 occupancy correlated with hundreds of transcripts that fell but not with equal numbers that rose with Cdx loss, indicating a predominantly activating role at intestinal cis-regulatory regions. Integrated consideration of a mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a master developmental regulator that activates tissue-specific genes. Cdx2 ChIP-seq in mouse villus, and gene expression data from Cdx1, Cdx2 and compound knockout mouse intestine

ORGANISM(S): Mus musculus

SUBMITTER: Michael Verzi 

PROVIDER: E-GEOD-24633 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Essential and redundant functions of caudal family proteins in activating adult intestinal genes.

Verzi Michael P MP   Shin Hyunjin H   Ho Li-Lun LL   Liu X Shirley XS   Shivdasani Ramesh A RA  

Molecular and cellular biology 20110314 10


Transcription factors that potently induce cell fate often remain expressed in the induced organ throughout life, but their requirements in adults are uncertain and varied. Mechanistically, it is unclear if they activate only tissue-specific genes or also directly repress heterologous genes. We conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null emb  ...[more]

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