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      PlantRegMap: charting functional regulatory maps in plants

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          Abstract

          With the goal of charting plant transcriptional regulatory maps (i.e. transcription factors (TFs), cis-elements and interactions between them), we have upgraded the TF-centred database PlantTFDB ( http://planttfdb.cbi.pku.edu.cn/) to a plant regulatory data and analysis platform PlantRegMap ( http://plantregmap.cbi.pku.edu.cn/) over the past three years. In this version, we updated the annotations for the previously collected TFs and set up a new section, ‘extended TF repertoires’ (TFext), to allow users prompt access to the TF repertoires of newly sequenced species. In addition to our regular TF updates, we are dedicated to updating the data on cis-elements and functional interactions between TFs and cis-elements. We established genome-wide conservation landscapes for 63 representative plants and then developed an algorithm, FunTFBS, to screen for functional regulatory elements and interactions by coupling the base-varied binding affinities of TFs with the evolutionary footprints on their binding sites. Using the FunTFBS algorithm and the conservation landscapes, we further identified over 20 million functional TF binding sites (TFBSs) and two million functional interactions for 21 346 TFs, charting the functional regulatory maps of these 63 plants. These resources are publicly available at PlantRegMap ( http://plantregmap.cbi.pku.edu.cn/) and a cloud-based mirror ( http://plantregmap.gao-lab.org/), providing the plant research community with valuable resources for decoding plant transcriptional regulatory systems.

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          Most cited references20

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          Sequencing and comparison of yeast species to identify genes and regulatory elements.

          Identifying the functional elements encoded in a genome is one of the principal challenges in modern biology. Comparative genomics should offer a powerful, general approach. Here, we present a comparative analysis of the yeast Saccharomyces cerevisiae based on high-quality draft sequences of three related species (S. paradoxus, S. mikatae and S. bayanus). We first aligned the genomes and characterized their evolution, defining the regions and mechanisms of change. We then developed methods for direct identification of genes and regulatory motifs. The gene analysis yielded a major revision to the yeast gene catalogue, affecting approximately 15% of all genes and reducing the total count by about 500 genes. The motif analysis automatically identified 72 genome-wide elements, including most known regulatory motifs and numerous new motifs. We inferred a putative function for most of these motifs, and provided insights into their combinatorial interactions. The results have implications for genome analysis of diverse organisms, including the human.
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            PlantTFDB 3.0: a portal for the functional and evolutionary study of plant transcription factors

            With the aim to provide a resource for functional and evolutionary study of plant transcription factors (TFs), we updated the plant TF database PlantTFDB to version 3.0 (http://planttfdb.cbi.pku.edu.cn). After refining the TF classification pipeline, we systematically identified 129 288 TFs from 83 species, of which 67 species have genome sequences, covering main lineages of green plants. Besides the abundant annotation provided in the previous version, we generated more annotations for identified TFs, including expression, regulation, interaction, conserved elements, phenotype information, expert-curated descriptions derived from UniProt, TAIR and NCBI GeneRIF, as well as references to provide clues for functional studies of TFs. To help identify evolutionary relationship among identified TFs, we assigned 69 450 TFs into 3924 orthologous groups, and constructed 9217 phylogenetic trees for TFs within the same families or same orthologous groups, respectively. In addition, we set up a TF prediction server in this version for users to identify TFs from their own sequences.
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              An expansive human regulatory lexicon encoded in transcription factor footprints

              Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNaseI, leaving nucleotide-resolution footprints. Using genomic DNaseI footprinting across 41 diverse cell and tissue types, we detected 45 million factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements. Here we show that this small genomic sequence compartment, roughly twice the size of the exome, encodes an expansive repertoire of conserved recognition sequences for DNA-binding proteins that nearly doubles the size of the human cis-regulatory lexicon. We find that genetic variants affecting allelic chromatin states are concentrated in footprints, and that these elements are preferentially sheltered from DNA methylation. High-resolution DNaseI cleavage patterns mirror nucleotide-level evolutionary conservation and track the crystallographic topography of protein-DNA interfaces, indicating that transcription factor structure has been evolutionarily imprinted on the human genome sequence. We identify a stereotyped 50 base-pair footprint that precisely defines the site of transcript origination within thousands of human promoters. Finally, we describe a large collection of novel regulatory factor recognition motifs that are highly conserved in both sequence and function, and exhibit cell-selective occupancy patterns that closely parallel major regulators of development, differentiation, and pluripotency.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                08 January 2020
                08 November 2019
                08 November 2019
                : 48
                : D1
                : D1104-D1113
                Affiliations
                [1 ] State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Center for Bioinformatics, Peking University , Beijing 100871, China
                [2 ] Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced Innovation Center for Genomics (ICG), Peking University , Beijing 100871, China
                [3 ] Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University , Beijing 100871, China
                Author notes
                To whom correspondence should be addressed. Tel: +86 10 6275 5206; Fax: +86 10 6275 5206; Email: gaog@ 123456mail.cbi.pku.edu.cn
                Correspondence may also be addressed to Jinpu Jin. Email: jinjp@ 123456mail.cbi.pku.edu.cn

                The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.

                Author information
                http://orcid.org/0000-0001-6470-8815
                Article
                gkz1020
                10.1093/nar/gkz1020
                7145545
                31701126
                62de6749-e6ca-4c58-a587-9c4a7021164d
                © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 21 October 2019
                : 17 October 2019
                : 29 August 2019
                Page count
                Pages: 10
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 1470330
                Funded by: China 863 Program
                Award ID: 2015AA020108
                Funded by: State Key Laboratory of Protein and Plant Gene Research 10.13039/501100011253
                Funded by: China Postdoctoral Science Foundation 10.13039/501100002858
                Award ID: 2014M560017
                Award ID: 2015T80015
                Funded by: Peking University and Peking-Tsinghua Center for Life Sciences
                Categories
                Database Issue

                Genetics
                Genetics

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