Open AccessCDK12 Is Necessary to Promote Epidermal Differentiation Through Transcription Elongation
Author(s) -
Jingting Li,
Manisha Tiwari,
Yifang Chen,
Sudjit Luanpitpong,
George L. Sen
Publication year - 2022
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1093/stmcls/sxac002
Subject(s) - biology , transcription factor , microbiology and biotechnology , cellular differentiation , elongation factor , elongation , rna polymerase ii , klf4 , transcription (linguistics) , epidermis (zoology) , gene expression , gene , genetics , rna , promoter , anatomy , ribosome , sox2 , linguistics , materials science , philosophy , ultimate tensile strength , metallurgy
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.