دورية أكاديمية
Divergent functions of histone acetyltransferases KAT2A and KAT2B in keratinocyte self-renewal and differentiation.
| العنوان: | Divergent functions of histone acetyltransferases KAT2A and KAT2B in keratinocyte self-renewal and differentiation. |
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| المؤلفون: | Walters BW; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore.; School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK., Tan TJ; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore., Tan CT; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore., Dube CT; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore.; School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK., Lee KT; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore., Koh J; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore., Ong YHB; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore., Tan VXH; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore., Jahan FRS; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore., Lim XN; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117596Singapore., Wan Y; Genome Institute of Singapore, 138672 Singapore., Lim CY; Epithelial Epigenetics and Development Laboratory, A*STAR Skin Research Labs, 308232 Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117596Singapore. |
| المصدر: | Journal of cell science [J Cell Sci] 2023 Jun 15; Vol. 136 (12). Date of Electronic Publication: 2023 Jun 21. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Company of Biologists Country of Publication: England NLM ID: 0052457 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9137 (Electronic) Linking ISSN: 00219533 NLM ISO Abbreviation: J Cell Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge : Company of Biologists Original Publication: London. |
| مواضيع طبية MeSH: | Histone Acetyltransferases*/genetics , Histone Acetyltransferases*/metabolism , Keratinocytes*/metabolism, Animals ; Cell Differentiation/genetics ; Skin/metabolism ; Epidermis/metabolism ; Mammals/metabolism |
| مستخلص: | The mammalian epidermis undergoes constant renewal, replenished by a pool of stem cells and terminal differentiation of their progeny. This is accompanied by changes in gene expression and morphology that are orchestrated, in part, by epigenetic modifiers. Here, we define the role of the histone acetyltransferase KAT2A in epidermal homeostasis and provide a comparative analysis that reveals key functional divergence with its paralog KAT2B. In contrast to the reported function of KAT2B in epidermal differentiation, KAT2A supports the undifferentiated state in keratinocytes. RNA-seq analysis of KAT2A- and KAT2B- depleted keratinocytes revealed dysregulated epidermal differentiation. Depletion of KAT2A led to premature expression of epidermal differentiation genes in the absence of inductive signals, whereas loss of KAT2B delayed differentiation. KAT2A acetyltransferase activity was indispensable in regulating epidermal differentiation gene expression. The metazoan-specific N terminus of KAT2A was also required to support its function in keratinocytes. We further showed that the interplay between KAT2A- and KAT2B-mediated regulation was important for normal cutaneous wound healing in vivo. Overall, these findings reveal a distinct mechanism in which keratinocytes use a pair of highly homologous histone acetyltransferases to support divergent functions in self-renewal and differentiation processes. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.) |
| فهرسة مساهمة: | Keywords: Chromatin; Epidermis; Histone acetyltransferases; Keratinocytes; Skin regeneration |
| المشرفين على المادة: | EC 2.3.1.48 (Histone Acetyltransferases) |
| تواريخ الأحداث: | Date Created: 20230601 Date Completed: 20230622 Latest Revision: 20230626 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1242/jcs.260723 |
| PMID: | 37259855 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1477-9137 |
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| DOI: | 10.1242/jcs.260723 |