Integrative PTEN Enhancer Discovery Reveals a New Model of Enhancer Organization.

التفاصيل البيبلوغرافية
العنوان: Integrative PTEN Enhancer Discovery Reveals a New Model of Enhancer Organization.
المؤلفون: Cerda-Smith CG; Department of Pharmacology and Cancer Biology, Duke University School of Medicine; Durham, NC 27710, USA., Hutchinson HM; Department of Pharmacology and Cancer Biology, Duke University School of Medicine; Durham, NC 27710, USA., Liu A; Department of Surgery, Duke University School of Medicine; Durham, NC 27710, USA., Goel VY; Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, 02139, USA.; Broad Institute; Cambridge, MA 02139, USA.; Koch Institute for Integrative Cancer Research; Cambridge, MA, 02139, USA., Sept C; Broad Institute; Cambridge, MA 02139, USA.; Department of Biostatistics, Harvard School of Public Health; Boston, MA 02215, USA., Kim H; Department of Radiation Oncology, Duke University School of Medicine; Durham, NC 27710, USA., Casaní-Galdón S; Broad Institute; Cambridge, MA 02139, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute; Boston, MA 02215, USA.; Departments of Cell Biology and Pathology, Harvard Medical School; Boston, MA 02114, USA., Burkman KG; Department of Radiation Oncology, Duke University School of Medicine; Durham, NC 27710, USA., Bassil CF; Department of Pharmacology and Cancer Biology, Duke University School of Medicine; Durham, NC 27710, USA., Hansen AS; Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, 02139, USA.; Broad Institute; Cambridge, MA 02139, USA.; Koch Institute for Integrative Cancer Research; Cambridge, MA, 02139, USA., Aryee MJ; Broad Institute; Cambridge, MA 02139, USA.; Department of Pathology, Harvard Medical School; Boston, MA 02114, USA.; Department of Data Science, Dana-Farber Cancer Institute; Boston, MA 02215, USA., Johnstone SE; Broad Institute; Cambridge, MA 02139, USA.; Department of Pathology, Dana-Farber Cancer Institute; Boston, MA 02215, USA., Eyler CE; Department of Radiation Oncology, Duke University School of Medicine; Durham, NC 27710, USA.; Duke Cancer Institute, Duke University School of Medicine; Durham, NC 27710, USA., Wood KC; Department of Pharmacology and Cancer Biology, Duke University School of Medicine; Durham, NC 27710, USA.; Duke Cancer Institute, Duke University School of Medicine; Durham, NC 27710, USA.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 21. Date of Electronic Publication: 2023 Sep 21.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: Enhancers possess both structural elements mediating promoter looping and functional elements mediating gene expression. Traditional models of enhancer-mediated gene regulation imply genomic overlap or immediate adjacency of these elements. We test this model by combining densely-tiled CRISPRa screening with nucleosome-resolution Region Capture Micro-C topology analysis. Using this integrated approach, we comprehensively define the cis -regulatory landscape for the tumor suppressor PTEN , identifying and validating 10 distinct enhancers and defining their 3D spatial organization. Unexpectedly, we identify several long-range functional enhancers whose promoter proximity is facilitated by chromatin loop anchors several kilobases away, and demonstrate that accounting for this spatial separation improves the computational prediction of validated enhancers. Thus, we propose a new model of enhancer organization incorporating spatial separation of essential functional and structural components.
معلومات مُعتمدة: K08 CA259623 United States CA NCI NIH HHS; DP2 GM140938 United States GM NIGMS NIH HHS; R33 CA257878 United States CA NCI NIH HHS; F30 CA247323 United States CA NCI NIH HHS; F32 CA268527 United States CA NCI NIH HHS; R01 CA207083 United States CA NCI NIH HHS; K08 CA263300 United States CA NCI NIH HHS; T32 GM007171 United States GM NIGMS NIH HHS
تواريخ الأحداث: Date Created: 20231003 Latest Revision: 20240718
رمز التحديث: 20240718
مُعرف محوري في PubMed: PMC10541578
DOI: 10.1101/2023.09.20.558459
PMID: 37786671
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2023.09.20.558459