Dataset Information

Expanded encyclopaedias of DNA elements in the human and mouse genomes.

ABSTRACT: The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE¹ and Roadmap Epigenomics² data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.

SUBMITTER: ENCODE Project Consortium

PROVIDER: S-EPMC7410828 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Expanded encyclopaedias of DNA elements in the human and mouse genomes.

Moore Jill E JE Purcaro Michael J MJ Pratt Henry E HE Epstein Charles B CB Shoresh Noam N Adrian Jessika J Kawli Trupti T Davis Carrie A CA Dobin Alexander A Kaul Rajinder R Halow Jessica J Van Nostrand Eric L EL Freese Peter P Gorkin David U DU Shen Yin Y He Yupeng Y Mackiewicz Mark M Pauli-Behn Florencia F Williams Brian A BA Mortazavi Ali A Keller Cheryl A CA Zhang Xiao-Ou XO Elhajjajy Shaimae I SI Huey Jack J Dickel Diane E DE Snetkova Valentina V Wei Xintao X Wang Xiaofeng X Rivera-Mulia Juan Carlos JC Rozowsky Joel J Zhang Jing J Chhetri Surya B SB Zhang Jialing J Victorsen Alec A White Kevin P KP Visel Axel A Yeo Gene W GW Burge Christopher B CB Lécuyer Eric E Gilbert David M DM Dekker Job J Rinn John J Mendenhall Eric M EM Ecker Joseph R JR Kellis Manolis M Klein Robert J RJ Noble William S WS Kundaje Anshul A Guigó Roderic R Farnham Peggy J PJ Cherry J Michael JM Myers Richard M RM Ren Bing B Graveley Brenton R BR Gerstein Mark B MB Pennacchio Len A LA Snyder Michael P MP Bernstein Bradley E BE Wold Barbara B Hardison Ross C RC Gingeras Thomas R TR Stamatoyannopoulos John A JA Weng Zhiping Z

Nature 20200729 7818

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these eff ...[more]

PMID: 32728249

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Project description:Recent genome-wide experiments in different eukaryotic genomes provide an unprecedented view of transcription factor (TF) binding locations and of nucleosome occupancy. These experiments revealed that a large fraction of TF binding events occur in regions where only a small number of specific TF binding sites (TFBSs) have been detected. Furthermore, in vitro protein-DNA binding measurements performed for hundreds of TFs indicate that TFs are bound with wide range of affinities to different DNA sequences that lack known consensus motifs. These observations have thus challenged the classical picture of specific protein-DNA binding and strongly suggest the existence of additional recognition mechanisms that affect protein-DNA binding preferences. We have previously demonstrated that repetitive DNA sequence elements characterized by certain symmetries statistically affect protein-DNA binding preferences. We call this binding mechanism nonconsensus protein-DNA binding in order to emphasize the point that specific consensus TFBSs do not contribute to this effect. In this paper, using the simple statistical mechanics model developed previously, we calculate the nonconsensus protein-DNA binding free energy for the entire C. elegans and D. melanogaster genomes. Using the available chromatin immunoprecipitation followed by sequencing (ChIP-seq) results on TF-DNA binding preferences for ~100 TFs, we show that DNA sequences characterized by low predicted free energy of nonconsensus binding have statistically higher experimental TF occupancy and lower nucleosome occupancy than sequences characterized by high free energy of nonconsensus binding. This is in agreement with our previous analysis performed for the yeast genome. We suggest therefore that nonconsensus protein-DNA binding assists the formation of nucleosome-free regions, as TFs outcompete nucleosomes at genomic locations with enhanced nonconsensus binding. In addition, here we perform a new, large-scale analysis using in vitro TF-DNA preferences obtained from the universal protein binding microarrays (PBM) for ~90 eukaryotic TFs belonging to 22 different DNA-binding domain types. As a result of this new analysis, we conclude that nonconsensus protein-DNA binding is a widespread phenomenon that significantly affects protein-DNA binding preferences and need not require the presence of consensus (specific) TFBSs in order to achieve genome-wide TF-DNA binding specificity.

Dataset Information

Expanded encyclopaedias of DNA elements in the human and mouse genomes.

Publications

Expanded encyclopaedias of DNA elements in the human and mouse genomes.

Similar Datasets

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