Atlas and developmental dynamics of mouse DNase I hypersensitive sites
Atlas and developmental dynamics of mouse DNase I hypersensitive sites
Abstract Early mammalian development is orchestrated by genome-encoded regulatory elements populated by a changing complement of regulatory factors, creating a dynamic chromatin landscape. To define the spatiotemporal organization of regulatory DNA landscapes during mouse development and maturation, we generated nucleotide-resolution DNA accessibility maps from 15 tissues sampled at 9 intervals spanning post-conception day 9.5 through early adult, and integrated these with 41 adult-stage DNase-seq profiles to create a global atlas of mouse regulatory DNA. Collectively, we delineated >1.8 million DNase I hypersensitive sites (DHSs), with the vast majority displaying temporal and tissue-selective patterning. Here we show that tissue regulatory DNA compartments show sharp embryonic-to-fetal transitions characterized by wholesale turnover of DHSs and progressive domination by a diminishing number of transcription factors. We show further that aligning mouse and human fetal development on a regulatory axis exposes disease-associated variation enriched in early intervals lacking human samples. Our results provide an expansive new resource for decoding mammalian developmental regulatory programs.
Reynolds Alex、Washington Ida、Halow Jessica、Lazar John、Lee Kristen、Ibarrientos Sean、Neri Fidencio、Haugen Eric、Rynes Eric、Dunn Douglas、Kaul Rajinder、Bender M.A.、Stamatoyannopoulos John A.、Breeze Charles E.、Diegel Morgan、Sandstrom Richard、Mercer Tim、Bates Daniel、Groudine Mark、Meuleman Wouter、Castillo Andres
Altius Institute for Biomedical SciencesDept. of Microbiology, Immunology and Cell Biology, West Virginia UniversityAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesDepartment of Pediatrics, University of Washington||Clinical Research Division, Fred Hutchinson Cancer Research CenterAltius Institute for Biomedical Sciences||Depts. of Genome Sciences and Medicine, University of WashingtonAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesAltius Institute for Biomedical SciencesDivision of Basic Sciences, Fred Hutchinson Cancer Research Center||Department of Radiation Oncology, University of WashingtonAltius Institute for Biomedical SciencesAltius Institute for Biomedical Sciences
遗传学分子生物学生物科学研究方法、生物科学研究技术
Reynolds Alex,Washington Ida,Halow Jessica,Lazar John,Lee Kristen,Ibarrientos Sean,Neri Fidencio,Haugen Eric,Rynes Eric,Dunn Douglas,Kaul Rajinder,Bender M.A.,Stamatoyannopoulos John A.,Breeze Charles E.,Diegel Morgan,Sandstrom Richard,Mercer Tim,Bates Daniel,Groudine Mark,Meuleman Wouter,Castillo Andres.Atlas and developmental dynamics of mouse DNase I hypersensitive sites[EB/OL].(2025-03-28)[2025-06-12].https://www.biorxiv.org/content/10.1101/2020.06.26.172718.点此复制
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