title: HOXB4 Gene Expression Is Regulated by CDX2 in Intestinal Epithelial Cells.
abstract: The mammalian Caudal-related homeobox transcription factor 2 (CDX2) plays a key role in the homeobox regulatory network and is essential in regulating the expression of several homeobox (HOX) genes during embryonic development, particularly in the gut. Genome-wide CDX2 chromatin immunoprecipitation analysis and expression data from Caco2 cells also suggests a role for CDX2 in the regulation of HOXB4 gene expression in the intestinal epithelium. Thus, the aim of this study was to investigate whether HOXB4 gene expression is regulated by CDX2 in the intestinal epithelium. We demonstrated binding of CDX2 to four different CDX2 binding sites in an enhancer region located upstream of the HOXB4 transcription start site. Mutations in the CDX2 binding sites reduced HOXB4 gene activity, and knock down of endogenous CDX2 expression by shRNA reduced HOXB4 gene expression. This is the first report demonstrating the CDX2 regulation of HOXB4 gene expression in the developed intestinal epithelium, indicating a possible role for HOXB4 in intestinal homeostasis.
authors.affiliation: Department of Science and Environment, Roskilde University, Roskilde, Denmark.|Department of Clinical Immunology, Naestved Hospital, Naestved, Region Zealand, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jørgensen
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Coskun
authors.affiliation: Department of Clinical Immunology, Naestved Hospital, Naestved, Region Zealand, Denmark.
authors.forename: Keld Mikkelsen
authors.initials: KM
authors.lastname: Homburg
authors.affiliation: Department of Clinical Immunology, Naestved Hospital, Naestved, Region Zealand, Denmark.
authors.forename: Ole B V
authors.initials: OB
authors.lastname: Pedersen
authors.affiliation: Department of Science and Environment, Roskilde University, Roskilde, Denmark.
authors.forename: Jesper T
authors.initials: JT
authors.lastname: Troelsen
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D000071616:CDX2 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000166:cytology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors