title: An integrative analysis of TFBS-clustered regions reveals new transcriptional regulation models on the accessible chromatin landscape.
abstract: DNase I hypersensitive sites (DHSs) define the accessible chromatin landscape and have revolutionised the discovery of distinct cis-regulatory elements in diverse organisms. Here, we report the first comprehensive map of human transcription factor binding site (TFBS)-clustered regions using Gaussian kernel density estimation based on genome-wide mapping of the TFBSs in 133 human cell and tissue types. Approximately 1.6 million distinct TFBS-clustered regions, collectively spanning 27.7% of the human genome, were discovered. The TFBS complexity assigned to each TFBS-clustered region was highly correlated with genomic location, cell selectivity, evolutionary conservation, sequence features, and functional roles. An integrative analysis of these regions using ENCODE data revealed transcription factor occupancy, transcriptional activity, histone modification, DNA methylation, and chromatin structures that varied based on TFBS complexity. Furthermore, we found that we could recreate lineage-branching relationships by simple clustering of the TFBS-clustered regions from terminally differentiated cells. Based on these findings, a model of transcriptional regulation determined by TFBS complexity is proposed.
authors: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Hebing
authors: H
authors: Chen
authors: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Hao
authors: H
authors: Li
authors: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Feng
authors: F
authors: Liu
authors: Department of Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Xiaofei
authors: X
authors: Zheng
authors: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Shengqi
authors: S
authors: Wang
authors: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Xiaochen
authors: X
authors: Bo
authors: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors: Wenjie
authors: W
authors: Shu
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D016208:Databases, Factual; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D015894:Genome, Human; D006657:Histones / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008745:Methylation; D008957:Models, Genetic; D012313:RNA / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors; D012313:RNA; D012319:RNA Polymerase II