Journal Article

Occupancy maps of 208 chromatin-associated proteins in one human cell type

Coppola, Candice J., Mackiewicz, Mark, Mendenhall, Eric M., Savic, Daniel, Partridge, E. Christopher, Jansen, Camden S., Newberry, Kimberly M., Brandsmeier, Laurel A., Dean, Emma C., Prokop, Jeremy W., Hardigan, Andrew A., Wold, Barbara J., Goh, Say-Tar, Meadows, Sarah K., Messer, C. Luke, Chhetri, Surya B., Ramaker, Ryne C., Jiang, Shan, Mortazavi, Ali, Myers, Richard M.

2020

Overview

Transcription factors are DNA-binding proteins that have key roles in gene regulation 1 , 2 . Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes 3 – 6 . However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP–seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium. ChIP–seq and CETCh–seq data are used to analyse binding maps for 208 transcription factors and other chromatin-associated proteins in a single human cell type, providing a comprehensive catalogue of the transcription factor landscape and gene regulatory networks in these cells.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 42/41 / 631/208/177 / 631/208/200 / 631/208/212/2019 / 631/45/147 / Analysis / Binding / Binding sites / Biological effects / Chromatin / Chromatin - genetics / Chromatin - metabolism / Chromatin Immunoprecipitation Sequencing / Chromosome mapping / Cofactors / Consortia / Datasets as Topic / Deoxyribonucleic acid / DNA / DNA-binding protein / DNA-Binding Proteins - metabolism / Encyclopedias / Enhancer Elements, Genetic - genetics / Enhancers / Experiments / Gene expression / Gene mapping / Gene regulation / Genomes / Hep G2 Cells / Human genome / Humanities and Social Sciences / Humans / Immunoprecipitation / Methods / Molecular Sequence Annotation / multidisciplinary / Next-generation sequencing / Nucleotide Motifs - genetics / Nucleotide sequence / Occupancy / Principal components analysis / Promoter Regions, Genetic - genetics / Promoters / Protein Binding / Proteins / Regulators / Regulatory Sequences, Nucleic Acid - genetics / RNA polymerase / Science / Science (multidisciplinary) / Transcription factors / Transcription Factors - metabolism