CDK12 Is Necessary to Promote Epidermal Differentiation ThroughTranscription Elongation
Issued Date
2022-04-01
Resource Type
ISSN
10665099
eISSN
15494918
Scopus ID
2-s2.0-85129779343
Pubmed ID
35325240
Journal Title
Stem Cells
Volume
40
Issue
4
Start Page
435
End Page
445
Rights Holder(s)
SCOPUS
Bibliographic Citation
Stem Cells Vol.40 No.4 (2022) , 435-445
Suggested Citation
Li J., Tiwari M., Chen Y., Luanpitpong S., Sen G.L. CDK12 Is Necessary to Promote Epidermal Differentiation ThroughTranscription Elongation. Stem Cells Vol.40 No.4 (2022) , 435-445. 445. doi:10.1093/stmcls/sxac002 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85969
Title
CDK12 Is Necessary to Promote Epidermal Differentiation ThroughTranscription Elongation
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
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.