bivalent-like chromatin markers are predictive for transcription start site distribution in humanbivalent-like染色质标记预测转录起始站点分布在人类.pdfVIP

Bivalent-Like Chromatin Markers Are Predictive for Transcription Start Site Distribution in Human 1,2,3 1 1,4 Zhihua Zhang , Xiaotu Ma , Michael Q. Zhang * 1 Department of Molecular Cell Biology, Center for Systems Biology, University of Texas at Dallas, Richardson, Texas, United States of America, 2 Center for Computational Biology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, People’s Republic of China, 3 Laboratory of Disease Genomics and Personalized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, People’s Republic of China, 4 Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing, China Abstract Deep sequencing of 59 capped transcripts has revealed a variety of transcription initiation patterns, from narrow, focused promoters to wide, broad promoters. Attempts have already been made to model empirically classified patterns, but virtually no quantitative models for transcription initiation have been reported. Even though both genetic and epigenetic elements have been associated with such patterns, the organization of regulatory elements is largely unknown. Here, linear regression models were derived from a pool of regulatory elements, including genomic DNA features, nucleosome organization, and histone modifications, to predict the distribution of transcription start sites (TSS). Importantly, models including both active and repressive histone modification markers, e.g. H3K4me3 and H4K20me1, were consistently found to be much more predictive than models with only single-type histone modificat