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TAD evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function.
Okhovat, Mariam; VanCampen, Jake; Nevonen, Kimberly A; Harshman, Lana; Li, Weiyu; Layman, Cora E; Ward, Samantha; Herrera, Jarod; Wells, Jackson; Sheng, Rory R; Mao, Yafei; Ndjamen, Blaise; Lima, Ana C; Vigh-Conrad, Katinka A; Stendahl, Alexandra M; Yang, Ran; Fedorov, Lev; Matthews, Ian R; Easow, Sarah A; Chan, Dylan K; Jan, Taha A; Eichler, Evan E; Rugonyi, Sandra; Conrad, Donald F; Ahituv, Nadav; Carbone, Lucia.
Affiliation
  • Okhovat M; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA. okhovat@ohsu.edu.
  • VanCampen J; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
  • Nevonen KA; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
  • Harshman L; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Li W; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • Layman CE; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Ward S; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • Herrera J; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
  • Wells J; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
  • Sheng RR; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
  • Mao Y; Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
  • Ndjamen B; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Lima AC; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • Vigh-Conrad KA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
  • Stendahl AM; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
  • Yang R; Histology and Light Microscopy Core Facility, Gladstone Institutes, San Francisco, CA, USA.
  • Fedorov L; Division of Genetics, Oregon National Primate Research Center, Beaverton, OR, USA.
  • Matthews IR; Division of Genetics, Oregon National Primate Research Center, Beaverton, OR, USA.
  • Easow SA; Division of Genetics, Oregon National Primate Research Center, Beaverton, OR, USA.
  • Chan DK; Division of Genetics, Oregon National Primate Research Center, Beaverton, OR, USA.
  • Jan TA; OHSU Transgenic Mouse Models Core Lab, Oregon Health and Science University, Portland, OR, USA.
  • Eichler EE; Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, CA, USA.
  • Rugonyi S; Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, CA, USA.
  • Conrad DF; Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, CA, USA.
  • Ahituv N; Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Carbone L; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Nat Commun ; 14(1): 8111, 2023 Dec 07.
Article in En | MEDLINE | ID: mdl-38062027
ABSTRACT
Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation. We find 14% of all human TAD boundaries to be shared among all eight species (ultraconserved), while 15% are human-specific. Ultraconserved TAD boundaries have stronger insulation strength, CTCF binding, and enrichment of older retrotransposons compared to species-specific boundaries. CRISPR-Cas9 knockouts of an ultraconserved boundary in a mouse model lead to tissue-specific gene expression changes and morphological phenotypes. Deletion of a human-specific boundary near the autism-related AUTS2 gene results in the upregulation of this gene in neurons. Overall, our study provides pertinent TAD boundary evolutionary conservation annotations and showcases the functional importance of TAD evolution.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genome / Genomics Limits: Animals / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2023 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genome / Genomics Limits: Animals / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2023 Document type: Article Affiliation country: