ArticleNature communications2022
CDK9 activity switch associated with AFF1 and HEXIM1 controls differentiation initiation from epidermal progenitors.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Research progress on the mechanisms of Panax ginseng and its active components in maintaining skin homeostasis and disease intervention.Chinese medicine · 2026Review
- Spatial and Single-Cell Transcriptomics Reveal Keratinocytes as Key Players in Vulvar Lichen Sclerosus Pathogenesis.The Journal of investigative dermatology · 2026Article
- Cell-type-specific RNA polymerase II activity maps in intact tissues provide a gateway to mammalian gene regulatory mechanisms in vivo.Developmental cell · 2026Article
- Disrupting CDK9 activity suppresses triple-negative breast cancer and is enhanced by EGFR Inhibition.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Unraveling the CDK9/PP2A/ERK Network in Transcriptional Pause Release and Complement Activation in KRAS-mutant Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Transcriptional elongation control in developmental gene expression, aging, and disease.Molecular cell · 2023Review
- A Comprehensive Comparison of Tissue Processing Methods for High-Quality MALDI Imaging of Lipids in Reconstructed Human Epidermis.Journal of the American Society for Mass Spectrometry · 2023Article
- Nucleoporin downregulation modulates progenitor differentiation independent of nuclear pore numbers.Communications biology · 2023Article
- NUP98 and RAE1 sustain progenitor function through HDAC-dependent chromatin targeting to escape from nucleolar localization.Communications biology · 2023Article
- Non-Healing Perianal Fistulas: A Clinical Model of Tissue Senescence Impairing Both Tissue Fibrosis and Regenerative Potential.Biomedicines · 2023Review
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Progenitors in epithelial tissues, such as human skin epidermis, continuously make fate decisions between self-renewal and differentiation. Here we show that the Super Elongation Complex (SEC) controls progenitor fate decisions by directly suppressing a group of "rapid response" genes, which feature high enrichment of paused Pol II in the progenitor state and robust Pol II elongation in differentiation. SEC's repressive role is dependent on the AFF1 scaffold, but not AFF4. In the progenitor state, AFF1-SEC associates with the HEXIM1-containing inactive CDK9 to suppress these rapid-response genes. A key rapid-response SEC target is ATF3, which promotes the upregulation of differentiation-activating transcription factors (GRHL3, OVOL1, PRDM1, ZNF750) to advance terminal differentiation. SEC peptidomimetic inhibitors or PKC signaling activates CDK9 and rapidly induces these transcription factors within hours in keratinocytes. Thus, our data suggest that the activity switch of SEC-associated CDK9 underlies the initial processes bifurcating progenitor fates between self-renewal and differentiation.
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