دورية أكاديمية
CDK12 Is Necessary to Promote Epidermal Differentiation Through Transcription Elongation.
| العنوان: | CDK12 Is Necessary to Promote Epidermal Differentiation Through Transcription Elongation. |
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| المؤلفون: | Li J; Institute of Precision Medicine, Department of Burns, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China., Tiwari M; Department of Dermatology and Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA., Chen Y; Department of Dermatology and Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA., Luanpitpong S; Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkoknoi, Bangkok, Thailand., Sen GL; Department of Dermatology and Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA. |
| المصدر: | Stem cells (Dayton, Ohio) [Stem Cells] 2022 Apr 29; Vol. 40 (4), pp. 435-445. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9304532 Publication Model: Print Cited Medium: Internet ISSN: 1549-4918 (Electronic) Linking ISSN: 10665099 NLM ISO Abbreviation: Stem Cells Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2022- : Oxford : Oxford University Press Original Publication: Dayton, OH : AlphaMed Press, c1993- |
| مواضيع طبية MeSH: | Cyclin-Dependent Kinases*/genetics , Cyclin-Dependent Kinases*/metabolism , RNA Polymerase II*/chemistry , RNA Polymerase II*/genetics , RNA Polymerase II*/metabolism, Cell Differentiation/genetics ; Humans ; Phosphorylation ; Transcription Factors/genetics ; Transcription Factors/metabolism |
| مستخلص: | Proper differentiation of the epidermis is essential to prevent water loss and to protect the body from the outside environment. Perturbations in this process can lead to a variety of skin diseases that impacts 1 in 5 people. While transcription factors that control epidermal differentiation have been well characterized, other aspects of transcription control such as elongation are poorly understood. Here we show that of the two cyclin-dependent kinases (CDK12 and CDK13), that are known to regulate transcription elongation, only CDK12 is necessary for epidermal differentiation. Depletion of CDK12 led to loss of differentiation gene expression and absence of skin barrier formation in regenerated human epidermis. CDK12 binds to genes that code for differentiation promoting transcription factors (GRHL3, KLF4, and OVOL1) and is necessary for their elongation. CDK12 is necessary for elongation by promoting Ser2 phosphorylation on the C-terminal domain of RNA polymerase II and the stabilization of binding of the elongation factor SPT6 to target genes. Our results suggest that control of transcription elongation by CDK12 plays a prominent role in adult cell fate decisions. (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.) |
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| معلومات مُعتمدة: | R01 AR081215 United States AR NIAMS NIH HHS; R01 AR066530 United States AR NIAMS NIH HHS; R01 CA269303 United States CA NCI NIH HHS; R01AR072590 United States NH NIH HHS; R01 CA225463 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: CDK12; CDK13; ChIP-Seq; GRHL1; GRHL3: KLF4; OVOL1; RNA polymerase II; SPT6; SUPT6H; differentiation; elongation; epidermis; keratinocytes; skin barrier; skin differentiation; stem cell; stratum corneum; transcription |
| المشرفين على المادة: | 0 (Transcription Factors) EC 2.7.11.22 (CDK12 protein, human) EC 2.7.11.22 (Cyclin-Dependent Kinases) EC 2.7.7.- (RNA Polymerase II) |
| تواريخ الأحداث: | Date Created: 20220324 Date Completed: 20220502 Latest Revision: 20240515 |
| رمز التحديث: | 20240515 |
| مُعرف محوري في PubMed: | PMC9199850 |
| DOI: | 10.1093/stmcls/sxac002 |
| PMID: | 35325240 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1549-4918 |
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| DOI: | 10.1093/stmcls/sxac002 |