PMID- 21402776 OWN - NLM STAT- MEDLINE DCOM- 20110627 LR - 20220330 IS - 1098-5549 (Electronic) IS - 0270-7306 (Print) IS - 0270-7306 (Linking) VI - 31 IP - 10 DP - 2011 May TI - Essential and redundant functions of caudal family proteins in activating adult intestinal genes. PG - 2026-39 LID - 10.1128/MCB.01250-10 [doi] AB - 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 embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was significantly accelerated in mice lacking both Cdx2 and its homolog Cdx1, with particular exaggeration of defects in villus enterocyte differentiation. Importantly, 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 transcription factor's mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a critical developmental regulator that activates tissue-specific genes. FAU - Verzi, Michael P AU - Verzi MP AD - Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. FAU - Shin, Hyunjin AU - Shin H FAU - Ho, Li-Lun AU - Ho LL FAU - Liu, X Shirley AU - Liu XS FAU - Shivdasani, Ramesh A AU - Shivdasani RA LA - eng SI - GEO/GSE24633 GR - 1K01DK088868-01/DK/NIDDK NIH HHS/United States GR - R01DK082889/DK/NIDDK NIH HHS/United States GR - K01 DK088868/DK/NIDDK NIH HHS/United States GR - R01HG4069/HG/NHGRI NIH HHS/United States GR - P50CA127003/CA/NCI NIH HHS/United States GR - R01 DK082889/DK/NIDDK NIH HHS/United States GR - R01 HG004069/HG/NHGRI NIH HHS/United States GR - P50 CA127003/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110314 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (CDX2 Transcription Factor) RN - 0 (Cdx1 protein, mouse) RN - 0 (Cdx2 protein, mouse) RN - 0 (Homeodomain Proteins) RN - 0 (Transcription Factors) SB - IM MH - Animals MH - CDX2 Transcription Factor MH - Cell Differentiation MH - Enterocytes/*physiology MH - Gene Expression MH - Gene Expression Regulation, Developmental MH - Homeodomain Proteins/*genetics/metabolism MH - Intestinal Mucosa/embryology/growth & development/*metabolism MH - Mice MH - Mice, Knockout MH - Microarray Analysis MH - Molecular Sequence Data MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transcription Factors/*genetics/metabolism MH - *Transcriptional Activation PMC - PMC3133364 EDAT- 2011/03/16 06:00 MHDA- 2011/06/28 06:00 PMCR- 2011/11/01 CRDT- 2011/03/16 06:00 PHST- 2011/03/16 06:00 [entrez] PHST- 2011/03/16 06:00 [pubmed] PHST- 2011/06/28 06:00 [medline] PHST- 2011/11/01 00:00 [pmc-release] AID - MCB.01250-10 [pii] AID - 1250-10 [pii] AID - 10.1128/MCB.01250-10 [doi] PST - ppublish SO - Mol Cell Biol. 2011 May;31(10):2026-39. doi: 10.1128/MCB.01250-10. Epub 2011 Mar 14.