Transcriptional repression and enhancer decommissioning silence cell cycle genes in postmitotic tissues.

Autor: Fogarty EA; Molecular, Cellular and Developmental Biology, University of Michigan, 1105 N. University Ave., Ann Arbor, MI 48109, USA., Buchert EM; Molecular, Cellular and Developmental Biology, University of Michigan, 1105 N. University Ave., Ann Arbor, MI 48109, USA., Ma Y; Molecular, Cellular and Developmental Biology, University of Michigan, 1105 N. University Ave., Ann Arbor, MI 48109, USA., Nicely AB; Molecular, Cellular and Developmental Biology, University of Michigan, 1105 N. University Ave., Ann Arbor, MI 48109, USA., Buttitta LA; Molecular, Cellular and Developmental Biology, University of Michigan, 1105 N. University Ave., Ann Arbor, MI 48109, USA.
Jazyk: angličtina
Zdroj: G3 (Bethesda, Md.) [G3 (Bethesda)] 2024 Oct 07; Vol. 14 (10).
DOI: 10.1093/g3journal/jkae203
Abstrakt: The mechanisms that maintain a non-cycling status in postmitotic tissues are not well understood. Many cell cycle genes have promoters and enhancers that remain accessible even when cells are terminally differentiated and in a non-cycling state, suggesting their repression must be maintained long term. In contrast, enhancer decommissioning has been observed for rate-limiting cell cycle genes in the Drosophila wing, a tissue where the cells die soon after eclosion, but it has been unclear if this also occurs in other contexts of terminal differentiation. In this study, we show that enhancer decommissioning also occurs at specific, rate-limiting cell cycle genes in the long-lived tissues of the Drosophila eye and brain, and we propose this loss of chromatin accessibility may help maintain a robust postmitotic state. We examined the decommissioned enhancers at specific rate-limiting cell cycle genes and showed that they encode for dynamic temporal and spatial expression patterns that include shared, as well as tissue-specific elements, resulting in broad gene expression with developmentally controlled temporal regulation. We extend our analysis to cell cycle gene expression and chromatin accessibility in the mammalian retina using a published dataset and find that the principles of cell cycle gene regulation identified in terminally differentiating Drosophila tissues are conserved in the differentiating mammalian retina. We propose a robust, non-cycling status is maintained in long-lived postmitotic tissues through a combination of stable repression at most cell cycle genes, alongside enhancer decommissioning at specific rate-limiting cell cycle genes.
Competing Interests: Conflicts of interest The author(s) declare no conflict of interest.
(© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)
Databáze: MEDLINE
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