Evidence map›Paper›PMID 35325240›Full record

ArticleStem cells (Dayton, Ohio)2022

CDK12 Is Necessary to Promote Epidermal Differentiation Through Transcription Elongation.

Jingting Li, Manisha Tiwari, Yifang Chen, Sudjit Luanpitpong, George L Sen

Open access · greenAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 54% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 3 countries.

Jingting LiInstitute of Precision Medicine, Department of Burns, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Manisha TiwariDepartment of Dermatology and Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA.
Yifang ChenDepartment of Dermatology and Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA.
Sudjit LuanpitpongSiriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkoknoi, Bangkok, Thailand.
George L SenDepartment of Dermatology and Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0003-1279-8550
University of California San Diego · USSiriraj Hospital · THSun Yat-sen University · CN

Funding

Regulators of Epidermal Growth and DifferentiationR01AR066530 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEN, GEORGE L · 2015 to 2025
$4.0M
Regulators of Epidermal Homeostasis and TumorigenesisR01CA225463 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GEORGE L SEN · 2019 to 2026
$2.4M
Regulation of epidermal growth and differentiation through mRNA exportR01AR081215 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GEORGE L SEN · 2022 to 2026
$2.2M
Post-Transcriptional Regulators of Epidermal Homeostasis and NeoplasiaR01AR072590 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEN, GEORGE L · 2018 to 2022
$1.9M
Regulation of Human Tumorigensis by Cancer Specific NXF1 Adaptor ProteinsR01CA269303 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GEORGE L SEN · 2022 to 2026
$1.8M
NCI NIH HHS R01 CA225463NCI NIH HHS R01 CA269303NIAMS NIH HHS R01 AR066530NIAMS NIH HHS R01 AR072590NIAMS NIH HHS R01 AR081215NIH HHS R01AR072590
6 · The paper itself

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.

Indexed as

Cyclin-Dependent KinasesRNA Polymerase IICell DifferentiationHumansPhosphorylationTranscription FactorsCDK12 protein, humanCyclin-Dependent KinasesRNA Polymerase IITranscription FactorsCDK12CDK13ChIP-SeqdifferentiationelongationepidermisGRHL1GRHL3: KLF4keratinocytesOVOL1RNA polymerase IIskin barrierskin differentiationSPT6stem cellstratum corneumSUPT6Htranscription

Identifiers

PMID35325240
PMCPMC9199850
OpenAlexW4206929815

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.