Understanding transcriptional regulation by integrative analysis of transcription factor binding data

Cheng, C., Alexander, R., Min, R. Q., Leng, J., Yip, K. Y., Rozowsky, J., Yan, K. K., Dong, X. J., Djebali, S., Ruan, Y. J., Davis, C. A., Carninci, P., Lassman, T., Gingeras, T. R., Guigo, R., Birney, E., Weng, Z. P., Snyder, M., Gerstein, M. (2012) Understanding transcriptional regulation by integrative analysis of transcription factor binding data. Genome Research, 22 (9). pp. 1658-1667. ISSN 1088-9051

URL: http://www.ncbi.nlm.nih.gov/pubmed/22955978
DOI: 10.1101/gr.136838.111

Abstract

Statistical models have been used to quantify the relationship between gene expression and transcription factor (TF) binding signals. Here we apply the models to the large-scale data generated by the ENCODE project to study transcriptional regulation by TFs. Our results reveal a notable difference in the prediction accuracy of expression levels of transcription start sites (TSSs) captured by different technologies and RNA extraction protocols. In general, the expression levels of TSSs with high CpG content are more predictable than those with low CpG content. For genes with alternative TSSs, the expression levels of downstream TSSs are more predictable than those of the upstream ones. Different TF categories and specific TFs vary substantially in their contributions to predicting expression. Between two cell lines, the differential expression of TSS can be precisely reflected by the difference of IF-binding signals in a quantitative manner, arguing against the conventional on-and-off model of IF binding. Finally, we explore the relationships between TF-binding signals and other chromatin features such as histone modifications and DNase hypersensitivity for determining expression. The models imply that these features regulate transcription in a highly coordinated manner.

Item Type: Paper
Uncontrolled Keywords: gene-expression human genome chip-seq chromatin microarray evolution networks elements mechanism proteins
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service
CSHL labs > Gingeras lab
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date Deposited: 31 Jan 2013 20:11
Last Modified: 04 Nov 2015 16:06
PMCID: PMC3431483
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26921

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