Genome-wide analysis of CDX2 binding in intestinal epithelial cells (Caco-2).
The CDX2 transcription factor is known to play a crucial role in inhibiting proliferation, promoting differentiation and the expression of intestinal specific genes in intestinal cells. The overall effect of CDX2 in intestinal cells has previously been investigated in conditional knock-out mice, revealing a critical role of CDX2 in the formation of the normal intestinal identity. The identification of direct targets of transcription factors is a key problem in the study of gene regulatory networks. The ChIP-seq technique combines chromatin immunoprecipitation (ChIP) with next generation sequencing resulting in a high throughput experimental method of identifying direct targets of specific transcription factors. The method was applied to CDX2, leading to the identification of the direct binding of CDX2 to several known and novel target genes in the intestinal cell. Examination of the transcript levels of selected genes verified the regulatory role of CDX2 binding. The results place CDX2 as a key node in a transcription factor network controlling the proliferation and differentiation of intestinal cells.
Boyd
Mette
M
Department of Cellular and Molecular Medicine, Panum Institute, Building 6.4, University of Copenhagen, Blegdamsvej 3. 2200 Copenhagen N, Denmark.
Hansen
Morten
M
Jensen
Tine G K
TG
Perearnau
Anna
A
Olsen
Anders K
AK
Bram
Lotte L
LL
Bak
Mads
M
Tommerup
Niels
N
Olsen
Jørgen
J
Troelsen
Jesper T
JT
D000071616:CDX2 Transcription Factor; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D015894:Genome, Human / Q000235:genetics*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006609:High Mobility Group Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000166:cytology*; D008565:Membrane Proteins / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D000071616:CDX2 Transcription Factor; C486328:HBP1 protein, human; C492164:HEPH protein, human; D051557:Hepatocyte Nuclear Factor 4; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D008666:Metalloendopeptidases; C053833:meprin A