Understanding transcriptional regulation by integrative analysis of transcription factor binding data
Open Access
- 5 September 2012
- journal article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 22 (9), 1658-1667
- https://doi.org/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 TF-binding signals in a quantitative manner, arguing against the conventional on-and-off model of TF 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.Keywords
This publication has 52 references indexed in Scilit:
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- Architecture of the human regulatory network derived from ENCODE dataNature, 2012
- Genome-wide protein–DNA binding dynamics suggest a molecular clutch for transcription factor functionNature, 2012
- Control of Embryonic Stem Cell Lineage Commitment by Core Promoter Factor, TAF3Cell, 2011
- Dynamic Exchange at Regulatory Elements during Chromatin Remodeling Underlies Assisted Loading MechanismCell, 2011
- Differential chromatin marking of introns and expressed exons by H3K36me3Nature Genetics, 2009
- RNA-Seq: a revolutionary tool for transcriptomicsNature Reviews Genetics, 2009
- A high-resolution atlas of nucleosome occupancy in yeastNature Genetics, 2007
- Chromatin Modifications and Their FunctionCell, 2007
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006