Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells
Publication Date
August 29, 2017
Authors
Colin R. Lickwar, J. Gray Camp, Matthew Weiser, Jordan L. Cocchiaro, et al
Volume
15
Issue
8
Pages
e2002054
DOI
https://dx.plos.org/10.1371/journal.pbio.2002054
Publisher URL
http://journals.plos.org/plosbiology/article?id=10.1371%2Fjournal.pbio.2002054
Scopus
85028662434
Mendeley
http://www.mendeley.com/research/genomic-dissection-conserved-transcriptional-regulation-intestinal-epithelial-cells
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Mendeley | Further Information

{"title"=>"Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells", "type"=>"journal", "authors"=>[{"first_name"=>"Colin R.", "last_name"=>"Lickwar", "scopus_author_id"=>"14630789900"}, {"first_name"=>"J. Gray", "last_name"=>"Camp", "scopus_author_id"=>"26638041600"}, {"first_name"=>"Matthew", "last_name"=>"Weiser", "scopus_author_id"=>"56029897400"}, {"first_name"=>"Jordan L.", "last_name"=>"Cocchiaro", "scopus_author_id"=>"12786029000"}, {"first_name"=>"David M.", "last_name"=>"Kingsley", "scopus_author_id"=>"7102314996"}, {"first_name"=>"Terrence S.", "last_name"=>"Furey", "scopus_author_id"=>"6602302257"}, {"first_name"=>"Shehzad Z.", "last_name"=>"Sheikh", "scopus_author_id"=>"14523641400"}, {"first_name"=>"John F.", "last_name"=>"Rawls", "scopus_author_id"=>"7006103676"}], "year"=>2017, "source"=>"PLoS Biology", "identifiers"=>{"pui"=>"618047117", "sgr"=>"85028662434", "issn"=>"15457885", "pmid"=>"28850571", "scopus"=>"2-s2.0-85028662434", "doi"=>"10.1371/journal.pbio.2002054", "isbn"=>"1111111111"}, "id"=>"ef0df5df-dc5f-3023-92d5-852195c4e924", "abstract"=>"The intestinal epithelium serves critical physiologic functions that are shared among all vertebrates. However, it is unknown how the transcriptional regulatory mechanisms underlying these functions have changed over the course of vertebrate evolution. We generated genome-wide mRNA and accessible chromatin data from adult intestinal epithelial cells (IECs) in zebrafish, stickleback, mouse, and human species to determine if conserved IEC functions are achieved through common transcriptional regulation. We found evidence for substantial common regulation and conservation of gene expression regionally along the length of the intestine from fish to mammals and identified a core set of genes comprising a vertebrate IEC signature. We also identified transcriptional start sites and other putative regulatory regions that are differentially accessible in IECs in all 4 species. Although these sites rarely showed sequence conservation from fish to mammals, surprisingly, they drove highly conserved IEC expression in a zebrafish reporter assay. Common putative transcription factor binding sites (TFBS) found at these sites in multiple species indicate that sequence conservation alone is insufficient to identify much of the functionally conserved IEC regulatory information. Among the rare, highly sequence-conserved, IEC-specific regulatory regions, we discovered an ancient enhancer upstream from her6/HES1 that is active in a distinct population of Notch-positive cells in the intestinal epithelium. Together, these results show how combining accessible chromatin and mRNA datasets with TFBS prediction and in vivo reporter assays can reveal tissue-specific regulatory information conserved across 420 million years of vertebrate evolution. We define an IEC transcriptional regulatory network that is shared between fish and mammals and establish an experimental platform for studying how evolutionarily distilled regulatory information commonly controls IEC development and physiology.", "link"=>"http://www.mendeley.com/research/genomic-dissection-conserved-transcriptional-regulation-intestinal-epithelial-cells", "reader_count"=>18, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>2, "Veterinary Science and Veterinary Medicine"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "group_count"=>0}

Scopus | Further Information

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