Chromatin organization changes during the establishment and maintenance of the postmitotic state

Abstract Background Genome organization changes during development as cells differentiate. Chromatin motion becomes increasingly constrained and heterochromatin clusters as cells become restricted in their developmental potential. These changes coincide with slowing of the cell cycle, which can also...

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Main Authors: Yiqin Ma, Laura Buttitta
Format: Article
Language:English
Published: BMC 2017-11-01
Series:Epigenetics & Chromatin
Subjects:
E2F
Online Access:http://link.springer.com/article/10.1186/s13072-017-0159-8
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spelling doaj-1a2b558fde464dc0bb403fddf9f03cd32020-11-25T00:40:53ZengBMCEpigenetics & Chromatin1756-89352017-11-0110112010.1186/s13072-017-0159-8Chromatin organization changes during the establishment and maintenance of the postmitotic stateYiqin Ma0Laura Buttitta1Department of Molecular, Cellular and Developmental Biology, University of MichiganDepartment of Molecular, Cellular and Developmental Biology, University of MichiganAbstract Background Genome organization changes during development as cells differentiate. Chromatin motion becomes increasingly constrained and heterochromatin clusters as cells become restricted in their developmental potential. These changes coincide with slowing of the cell cycle, which can also influence chromatin organization and dynamics. Terminal differentiation is often coupled with permanent exit from the cell cycle, and existing data suggest a close relationship between a repressive chromatin structure and silencing of the cell cycle in postmitotic cells. Heterochromatin clustering could also contribute to stable gene repression to maintain terminal differentiation or cell cycle exit, but whether clustering is initiated by differentiation, cell cycle changes, or both is unclear. Here we examine the relationship between chromatin organization, terminal differentiation and cell cycle exit. Results We focused our studies on the Drosophila wing, where epithelial cells transition from active proliferation to a postmitotic state in a temporally controlled manner. We find there are two stages of G0 in this tissue, a flexible G0 period where cells can be induced to reenter the cell cycle under specific genetic manipulations and a state we call “robust,” where cells become strongly refractory to cell cycle reentry. Compromising the flexible G0 by driving ectopic expression of cell cycle activators causes a global disruption of the clustering of heterochromatin-associated histone modifications such as H3K27 trimethylation and H3K9 trimethylation, as well as their associated repressors, Polycomb and heterochromatin protein 1 (HP1). However, this disruption is reversible. When cells enter a robust G0 state, even in the presence of ectopic cell cycle activity, clustering of heterochromatin-associated modifications is restored. If cell cycle exit is bypassed, cells in the wing continue to terminally differentiate, but heterochromatin clustering is severely disrupted. Heterochromatin-dependent gene silencing does not appear to be required for cell cycle exit, as compromising the H3K27 methyltransferase Enhancer of zeste, and/or HP1 cannot prevent the robust cell cycle exit, even in the face of normally oncogenic cell cycle activities. Conclusions Heterochromatin clustering during terminal differentiation is a consequence of cell cycle exit, rather than differentiation. Compromising heterochromatin-dependent gene silencing does not disrupt cell cycle exit.http://link.springer.com/article/10.1186/s13072-017-0159-8DrosophilaCell cycle exitE2FHistone modificationsHeterochromatin binding proteins
collection DOAJ
language English
format Article
sources DOAJ
author Yiqin Ma
Laura Buttitta
spellingShingle Yiqin Ma
Laura Buttitta
Chromatin organization changes during the establishment and maintenance of the postmitotic state
Epigenetics & Chromatin
Drosophila
Cell cycle exit
E2F
Histone modifications
Heterochromatin binding proteins
author_facet Yiqin Ma
Laura Buttitta
author_sort Yiqin Ma
title Chromatin organization changes during the establishment and maintenance of the postmitotic state
title_short Chromatin organization changes during the establishment and maintenance of the postmitotic state
title_full Chromatin organization changes during the establishment and maintenance of the postmitotic state
title_fullStr Chromatin organization changes during the establishment and maintenance of the postmitotic state
title_full_unstemmed Chromatin organization changes during the establishment and maintenance of the postmitotic state
title_sort chromatin organization changes during the establishment and maintenance of the postmitotic state
publisher BMC
series Epigenetics & Chromatin
issn 1756-8935
publishDate 2017-11-01
description Abstract Background Genome organization changes during development as cells differentiate. Chromatin motion becomes increasingly constrained and heterochromatin clusters as cells become restricted in their developmental potential. These changes coincide with slowing of the cell cycle, which can also influence chromatin organization and dynamics. Terminal differentiation is often coupled with permanent exit from the cell cycle, and existing data suggest a close relationship between a repressive chromatin structure and silencing of the cell cycle in postmitotic cells. Heterochromatin clustering could also contribute to stable gene repression to maintain terminal differentiation or cell cycle exit, but whether clustering is initiated by differentiation, cell cycle changes, or both is unclear. Here we examine the relationship between chromatin organization, terminal differentiation and cell cycle exit. Results We focused our studies on the Drosophila wing, where epithelial cells transition from active proliferation to a postmitotic state in a temporally controlled manner. We find there are two stages of G0 in this tissue, a flexible G0 period where cells can be induced to reenter the cell cycle under specific genetic manipulations and a state we call “robust,” where cells become strongly refractory to cell cycle reentry. Compromising the flexible G0 by driving ectopic expression of cell cycle activators causes a global disruption of the clustering of heterochromatin-associated histone modifications such as H3K27 trimethylation and H3K9 trimethylation, as well as their associated repressors, Polycomb and heterochromatin protein 1 (HP1). However, this disruption is reversible. When cells enter a robust G0 state, even in the presence of ectopic cell cycle activity, clustering of heterochromatin-associated modifications is restored. If cell cycle exit is bypassed, cells in the wing continue to terminally differentiate, but heterochromatin clustering is severely disrupted. Heterochromatin-dependent gene silencing does not appear to be required for cell cycle exit, as compromising the H3K27 methyltransferase Enhancer of zeste, and/or HP1 cannot prevent the robust cell cycle exit, even in the face of normally oncogenic cell cycle activities. Conclusions Heterochromatin clustering during terminal differentiation is a consequence of cell cycle exit, rather than differentiation. Compromising heterochromatin-dependent gene silencing does not disrupt cell cycle exit.
topic Drosophila
Cell cycle exit
E2F
Histone modifications
Heterochromatin binding proteins
url http://link.springer.com/article/10.1186/s13072-017-0159-8
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AT laurabuttitta chromatinorganizationchangesduringtheestablishmentandmaintenanceofthepostmitoticstate
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