Author:
Kundaje Anshul,Kyriazopoulou-Panagiotopoulou Sofia,Libbrecht Max,Smith Cheryl L.,Raha Debasish,Winters Elliott E.,Johnson Steven M.,Snyder Michael,Batzoglou Serafim,Sidow Arend
Abstract
Gene regulation at functional elements (e.g., enhancers, promoters, insulators) is governed by an interplay of nucleosome remodeling, histone modifications, and transcription factor binding. To enhance our understanding of gene regulation, the ENCODE Consortium has generated a wealth of ChIP-seq data on DNA-binding proteins and histone modifications. We additionally generated nucleosome positioning data on two cell lines, K562 and GM12878, by MNase digestion and high-depth sequencing. Here we relate 14 chromatin signals (12 histone marks, DNase, and nucleosome positioning) to the binding sites of 119 DNA-binding proteins across a large number of cell lines. We developed a new method for unsupervised pattern discovery, the Clustered AGgregation Tool (CAGT), which accounts for the inherent heterogeneity in signal magnitude, shape, and implicit strand orientation of chromatin marks. We applied CAGT on a total of 5084 data set pairs to obtain an exhaustive catalog of high-resolution patterns of histone modifications and nucleosome positioning signals around bound transcription factors. Our analyses reveal extensive heterogeneity in how histone modifications are deposited, and how nucleosomes are positioned around binding sites. With the exception of the CTCF/cohesin complex, asymmetry of nucleosome positioning is predominant. Asymmetry of histone modifications is also widespread, for all types of chromatin marks examined, including promoter, enhancer, elongation, and repressive marks. The fine-resolution signal shapes discovered by CAGT unveiled novel correlation patterns between chromatin marks, nucleosome positioning, and sequence content. Meta-analyses of the signal profiles revealed a common vocabulary of chromatin signals shared across multiple cell lines and binding proteins.
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics (clinical),Genetics
Reference31 articles.
1. High-Resolution Profiling of Histone Methylations in the Human Genome
2. Djebali S , Davis CA , Merkel A , Dobin A , Lassmann T , Mortazavi AM , Tanzer A , Lagarde J , Lin W , Schlesinger F , . 2012. Landscape of transcription in human cells. Nature (in press).
3. The ENCODE Project Consortium. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature (in press).
4. Discovery and characterization of chromatin states for systematic annotation of the human genome
5. The Insulator Binding Protein CTCF Positions 20 Nucleosomes around Its Binding Sites across the Human Genome
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