دورية أكاديمية
أعرض في EDS

Systematic dissection of coding exons at single nucleotide resolution supports an additional role in cell-specific transcriptional regulation.

التفاصيل البيبلوغرافية
العنوان: Systematic dissection of coding exons at single nucleotide resolution supports an additional role in cell-specific transcriptional regulation.
المؤلفون: Birnbaum RY; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America; Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America; Department of Life Sciences, Ben-Gurion University at the Negev, Beer-Sheva, Israel., Patwardhan RP; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America., Kim MJ; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America; Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America., Findlay GM; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America., Martin B; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America., Zhao J; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America; Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America; Key Laboratory of Advanced Control and Optimization for Chemical Processes of the Ministry of Education, East China University of Science and Technology, Shanghai, China., Bell RJ; Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America; Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America; Biomedical Sciences (BMS) Graduate Program, University of California San Francisco, San Francisco, California, United States of America., Smith RP; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America; Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America., Ku AA; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America; Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America., Shendure J; Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America., Ahituv N; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America; Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
المصدر: PLoS genetics [PLoS Genet] 2014 Oct 23; Vol. 10 (10), pp. e1004592. Date of Electronic Publication: 2014 Oct 23 (Print Publication: 2014).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Enhancer Elements, Genetic*, Adaptor Proteins, Signal Transducing/*genetics , Exons/*genetics , Membrane Transport Proteins/*genetics , PPAR gamma/*genetics , Receptors, LDL/*genetics, Animals ; Binding Sites ; Gene Expression Regulation ; HeLa Cells ; Humans ; Liver/metabolism ; Mice ; Mutation, Missense ; Polymorphism, Single Nucleotide ; RNA Splicing/genetics ; Transcription Factors/biosynthesis
مستخلص: In addition to their protein coding function, exons can also serve as transcriptional enhancers. Mutations in these exonic-enhancers (eExons) could alter both protein function and transcription. However, the functional consequence of eExon mutations is not well known. Here, using massively parallel reporter assays, we dissect the enhancer activity of three liver eExons (SORL1 exon 17, TRAF3IP2 exon 2, PPARG exon 6) at single nucleotide resolution in the mouse liver. We find that both synonymous and non-synonymous mutations have similar effects on enhancer activity and many of the deleterious mutation clusters overlap known liver-associated transcription factor binding sites. Carrying a similar massively parallel reporter assay in HeLa cells with these three eExons found differences in their mutation profiles compared to the liver, suggesting that enhancers could have distinct operating profiles in different tissues. Our results demonstrate that eExon mutations could lead to multiple phenotypes by disrupting both the protein sequence and enhancer activity and that enhancers can have distinct mutation profiles in different cell types.
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معلومات مُعتمدة: R01HG005058 United States HG NHGRI NIH HHS; 1R01NS079231 United States NS NINDS NIH HHS; R01 HD059862 United States HD NICHD NIH HHS; GM008568 United States GM NIGMS NIH HHS; U01 GM061390 United States GM NIGMS NIH HHS; R01 HG006768 United States HG NHGRI NIH HHS; T32 GM008568 United States GM NIGMS NIH HHS; T32 GM007266 United States GM NIGMS NIH HHS; R01 DK090382 United States DK NIDDK NIH HHS; T32 GM007175 United States GM NIGMS NIH HHS; R01 HG005058 United States HG NHGRI NIH HHS; 1R01HG006768 United States HG NHGRI NIH HHS; 1R01DK090382 United States DK NIDDK NIH HHS; R01 NS079231 United States NS NINDS NIH HHS; U19 GM061390 United States GM NIGMS NIH HHS; R01HD059862 United States HD NICHD NIH HHS
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Membrane Transport Proteins)
0 (PPAR gamma)
0 (Receptors, LDL)
0 (Sorl1 protein, mouse)
0 (Traf3ip2 protein, mouse)
0 (Transcription Factors)
تواريخ الأحداث: Date Created: 20141024 Date Completed: 20150702 Latest Revision: 20211021
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4207465
DOI: 10.1371/journal.pgen.1004592
PMID: 25340400
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7404
DOI:10.1371/journal.pgen.1004592