دورية أكاديمية
أعرض في EDS

SPT6 promotes epidermal differentiation and blockade of an intestinal-like phenotype through control of transcriptional elongation.

التفاصيل البيبلوغرافية
العنوان: SPT6 promotes epidermal differentiation and blockade of an intestinal-like phenotype through control of transcriptional elongation.
المؤلفون: Li J; Department of Dermatology, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA., Xu X; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA., Tiwari M; Department of Dermatology, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA., Chen Y; Department of Dermatology, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA., Fuller M; Departments of Medicine and Cellular and Molecular Medicine, HUMANOID Center of Research Excellence, University of California, San Diego, La Jolla, CA, USA.; Department of Pathology, HUMANOID Center of Research Excellence, University of California, San Diego, La Jolla, CA, USA., Bansal V; Department of Dermatology, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA., Tamayo P; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.; Division of Medical Genetics, School of Medicine, University of California, San Diego, La Jolla, CA, USA., Das S; Department of Pathology, HUMANOID Center of Research Excellence, University of California, San Diego, La Jolla, CA, USA., Ghosh P; Departments of Medicine and Cellular and Molecular Medicine, HUMANOID Center of Research Excellence, University of California, San Diego, La Jolla, CA, USA., Sen GL; Department of Dermatology, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA. gsen@health.ucsd.edu.
المصدر: Nature communications [Nat Commun] 2021 Feb 04; Vol. 12 (1), pp. 784. Date of Electronic Publication: 2021 Feb 04.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Transcription Elongation, Genetic*, Cell Differentiation/*genetics , Epidermis/*physiology , Transcription Factors/*metabolism, Adult Stem Cells/physiology ; Cell Transdifferentiation/genetics ; Cells, Cultured ; Chromatin Immunoprecipitation Sequencing ; Gene Knockdown Techniques ; Humans ; Infant, Newborn ; Keratinocytes ; Male ; Primary Cell Culture ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; RNA, Small Interfering/metabolism ; RNA-Seq ; Tissue Culture Techniques ; Transcription Factors/genetics ; Tumor Suppressor Proteins/metabolism
مستخلص: In adult tissue, stem and progenitor cells must tightly regulate the balance between proliferation and differentiation to sustain homeostasis. How this exquisite balance is achieved is an area of active investigation. Here, we show that epidermal genes, including ~30% of induced differentiation genes already contain stalled Pol II at the promoters in epidermal stem and progenitor cells which is then released into productive transcription elongation upon differentiation. Central to this process are SPT6 and PAF1 which are necessary for the elongation of these differentiation genes. Upon SPT6 or PAF1 depletion there is a loss of human skin differentiation and stratification. Unexpectedly, loss of SPT6 also causes the spontaneous transdifferentiation of epidermal cells into an intestinal-like phenotype due to the stalled transcription of the master regulator of epidermal fate P63. Our findings suggest that control of transcription elongation through SPT6 plays a prominent role in adult somatic tissue differentiation and the inhibition of alternative cell fate choices.
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معلومات مُعتمدة: R01 CA238042 United States CA NCI NIH HHS; U24 CA248457 United States CA NCI NIH HHS; R01 CA100768 United States CA NCI NIH HHS; UG3 TR003355 United States TR NCATS NIH HHS; U24 CA220341 United States CA NCI NIH HHS; R01 AR072590 United States AR NIAMS NIH HHS; R01 CA225463 United States CA NCI NIH HHS; UG3 TR002968 United States TR NCATS NIH HHS; U01 CA217885 United States CA NCI NIH HHS; R01 AR066530 United States AR NIAMS NIH HHS; R01 DK107585 United States DK NIDDK NIH HHS; S10 OD026929 United States OD NIH HHS; R01 AI141630 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (PAF1 protein, human)
0 (RNA, Small Interfering)
0 (SUPT6H protein, human)
0 (TP63 protein, human)
0 (Transcription Factors)
0 (Tumor Suppressor Proteins)
EC 2.7.7.- (RNA Polymerase II)
تواريخ الأحداث: Date Created: 20210205 Date Completed: 20210219 Latest Revision: 20240130
رمز التحديث: 20240130
مُعرف محوري في PubMed: PMC7862286
DOI: 10.1038/s41467-021-21067-w
PMID: 33542242
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-021-21067-w