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Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants
The nuclear lamina (NL) lines the inner nuclear membrane. This extensive protein network organizes chromatin and contributes to the regulation of transcription, DNA replication, and repair. Lap2-emerin-MAN1 domain (LEM-D) proteins are key members of the NL, representing proteins that connect the NL...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210273/ https://www.ncbi.nlm.nih.gov/pubmed/34893833 http://dx.doi.org/10.1093/g3journal/jkab408 |
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author | Kitzman, Samuel Cole Duan, Tingting Pufall, Miles A Geyer, Pamela K |
author_facet | Kitzman, Samuel Cole Duan, Tingting Pufall, Miles A Geyer, Pamela K |
author_sort | Kitzman, Samuel Cole |
collection | PubMed |
description | The nuclear lamina (NL) lines the inner nuclear membrane. This extensive protein network organizes chromatin and contributes to the regulation of transcription, DNA replication, and repair. Lap2-emerin-MAN1 domain (LEM-D) proteins are key members of the NL, representing proteins that connect the NL to the genome through shared interactions with the chromatin-binding protein Barrier-to-Autointegration Factor (BAF). Functions of the LEM-D protein emerin and BAF are essential during Drosophila melanogaster oogenesis. Indeed, loss of either emerin or BAF blocks germ cell development and causes loss of germline stem cells, defects linked to the deformation of NL structure, and non-canonical activation of Checkpoint kinase 2 (Chk2). Here, we investigate the contributions of emerin and BAF to gene expression in the ovary. Profiling RNAs from emerin and baf mutant ovaries revealed that nearly all baf misregulated genes were shared with emerin mutants, defining a set of NL-regulated genes. Strikingly, loss of Chk2 restored the expression of most NL-regulated genes, identifying a large class of Chk2-dependent genes (CDGs). Nonetheless, some genes remained misexpressed upon Chk2 loss, identifying a smaller class of emerin-dependent genes (EDGs). Properties of EDGs suggest a shared role for emerin and BAF in the repression of developmental genes. Properties of CDGs demonstrate that Chk2 activation drives global misexpression of genes in the emerin and baf mutant backgrounds. Notably, CDGs were found upregulated in lamin-B mutant backgrounds. These observations predict that Chk2 activation might have a general role in gene expression changes found in NL-associated diseases, such as laminopathies. |
format | Online Article Text |
id | pubmed-9210273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-92102732022-06-21 Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants Kitzman, Samuel Cole Duan, Tingting Pufall, Miles A Geyer, Pamela K G3 (Bethesda) Investigation The nuclear lamina (NL) lines the inner nuclear membrane. This extensive protein network organizes chromatin and contributes to the regulation of transcription, DNA replication, and repair. Lap2-emerin-MAN1 domain (LEM-D) proteins are key members of the NL, representing proteins that connect the NL to the genome through shared interactions with the chromatin-binding protein Barrier-to-Autointegration Factor (BAF). Functions of the LEM-D protein emerin and BAF are essential during Drosophila melanogaster oogenesis. Indeed, loss of either emerin or BAF blocks germ cell development and causes loss of germline stem cells, defects linked to the deformation of NL structure, and non-canonical activation of Checkpoint kinase 2 (Chk2). Here, we investigate the contributions of emerin and BAF to gene expression in the ovary. Profiling RNAs from emerin and baf mutant ovaries revealed that nearly all baf misregulated genes were shared with emerin mutants, defining a set of NL-regulated genes. Strikingly, loss of Chk2 restored the expression of most NL-regulated genes, identifying a large class of Chk2-dependent genes (CDGs). Nonetheless, some genes remained misexpressed upon Chk2 loss, identifying a smaller class of emerin-dependent genes (EDGs). Properties of EDGs suggest a shared role for emerin and BAF in the repression of developmental genes. Properties of CDGs demonstrate that Chk2 activation drives global misexpression of genes in the emerin and baf mutant backgrounds. Notably, CDGs were found upregulated in lamin-B mutant backgrounds. These observations predict that Chk2 activation might have a general role in gene expression changes found in NL-associated diseases, such as laminopathies. Oxford University Press 2021-12-10 /pmc/articles/PMC9210273/ /pubmed/34893833 http://dx.doi.org/10.1093/g3journal/jkab408 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigation Kitzman, Samuel Cole Duan, Tingting Pufall, Miles A Geyer, Pamela K Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants |
title | Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants |
title_full | Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants |
title_fullStr | Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants |
title_full_unstemmed | Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants |
title_short | Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants |
title_sort | checkpoint activation drives global gene expression changes in drosophila nuclear lamina mutants |
topic | Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210273/ https://www.ncbi.nlm.nih.gov/pubmed/34893833 http://dx.doi.org/10.1093/g3journal/jkab408 |
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