Faculty Collaboration Database

Identification of an OCT4 and SRY regulatory module using integrated computational and experimental genomics approaches. Genome Res 2007 Jun;17(6):807-17

Date

06/15/2007

Pubmed ID

17567999

Pubmed Central ID

PMC1891340

DOI

10.1101/gr.6006107

Scopus ID

2-s2.0-34250369235 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

ChIP-chip studies have revealed that many in vivo binding sites have a weak match to the consensus sequence for the transcription factor being analyzed. Possible explanations for these observations include (1) the in vitro-derived consensus site does not represent the in vivo binding site and/or (2) the factor is recruited to a weak binding site via interaction with another protein. To address these possibilities, we developed an approach (ChIPMotifs) that incorporates a bootstrap resampling method to statistically infer the optimal cutoff threshold for a position weight matrix (PWM) of a motif identified from ChIP-chip data by ab initio motif discovery programs. Using OCT4 ChIP-chip data and the ChIPMotifs approach, we first developed a refined OCT4 PWM. We then used the refined PWM and a ChIPModules approach to identify transcription factors colocalizing with OCT4 in Ntera2 testicular embryonal carcinoma cells. We found that the consensus binding site for SRY, a transcription factor critical for testis development, colocalizes with the OCT4 PWM. To further characterize the relationship between OCT4 and SRY, we performed ChIP-chip experiments with human promoter microarrays, and found that 49% of the top approximately 1000 OCT4 target promoters were also bound by SRY. This analysis represents the first identification of SRY target promoters. Interestingly, we determined that promoters bound by OCT4 and SRY, but not those bound by SRY alone, were also bound by the transcriptional repressor KAP1. Our studies not only validate the ChIPMotifs and ChIPModules combinatorial approach but also identify a possible new regulatory partner of OCT4.

Author List

Jin VX, O'Geen H, Iyengar S, Green R, Farnham PJ

Author

Victor X. Jin PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Computational Biology
DNA-Binding Proteins
Humans
Male
Octamer Transcription Factor-3
Oligonucleotide Array Sequence Analysis
Organogenesis
Repressor Proteins
Response Elements
Sequence Analysis, DNA
Sex-Determining Region Y Protein
Software
Testis
Tripartite Motif-Containing Protein 28