Study of the role of chromatin-remodeling factor SWI/SNF in neuronal processes in Drosophila
- Authors: Deev R.V.1, Chmykhalo V.K.1, Stepanov N.G.1,2, Lebedeva L.A.1, Shidlovskii Y.V.1,2
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Affiliations:
- Institute of Gene Biology of the Russian Academy of Sciences
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
- Issue: Vol 18, No 4 (2023)
- Pages: 460-461
- Section: Conference proceedings
- URL: https://journals.rcsi.science/2313-1829/article/view/256243
- DOI: https://doi.org/10.17816/gc623247
- ID: 256243
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Abstract
SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that regulate the expression of numerous genes through the use of at least 15 subunits. The composition of these complexes is diverse, a result of combinatory assembly of subunits from homologous families with a variety of additional functions. During neurogenesis, researchers have identified distinctive SWI/SNF complexes that are specific to various stages of development. These complexes were detected in stem cells, neuronal progenitor cells, and postmitotic differentiated neurons. Notably, SWI/SNF complexes specific to neuronal progenitor cells are essential for regulating their division. SWI/SNF complexes are critical for adult brain plasticity in neurons and contribute to the regulatory genetic mechanisms that underlie higher neural activity, especially in learning and memory processes. However, the epigenetic regulation of gene expression in neurons remains insufficiently understood.
Mutations in complex subunits result in the development of pathologies. For instance, ARID1A and ARID1B subunit mutations in humans cause Coffin–Siris syndrome, which is a rare congenital multisystem genetic disease primarily characterized by developmental disabilities and intellectual disability. Currently, there are challenges in creating model systems to study Coffin–Siris syndrome. Drosophila has shown promise as a model organism due to its extensive research and suitability in studying neurodevelopmental pathologies. It is a cost-effective species that facilitates tracking of both species-specific features and general patterns for abnormality types. Additionally, Drosophila serves as a model organism due to its abundance of orthologous genes that lead to neuronal developmental abnormalities in humans. Notably, the knockdown of genes that encode subunit complexes in Drosophila produces a noticeable decline in long-term memory formation.
In this study, we examine the involvement of SAYP and osa complex subunits in different molecular mechanisms in Drosophila brain neurons. We use multiple strategies to alter the levels of SAYP and osa factors, such as tissue-specific knockdown, tissue-specific protein degradation, and null allele production. Using the CRISPR/Cas9 technique, we generated novel alleles of the osa and SAYP genes that encode operational proteins which can be selectively degraded at specific times and in specific tissues. We examine the changes in gene expression profiles, chromatin states, and the participation of transcription factors on chromatin, as well as DNA integrity alterations, upon removal of these factors from neurons. We are conducting research on the long-term memory of adult flies and neurogenesis at different developmental stages. Our aim is to gain insight into the role of the epigenetic regulator SWI/SNF in the development of nervous system pathologies and its involvement in the development and functioning of higher eukaryotic nervous systems.
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Full Text
SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that regulate the expression of numerous genes through the use of at least 15 subunits. The composition of these complexes is diverse, a result of combinatory assembly of subunits from homologous families with a variety of additional functions. During neurogenesis, researchers have identified distinctive SWI/SNF complexes that are specific to various stages of development. These complexes were detected in stem cells, neuronal progenitor cells, and postmitotic differentiated neurons. Notably, SWI/SNF complexes specific to neuronal progenitor cells are essential for regulating their division. SWI/SNF complexes are critical for adult brain plasticity in neurons and contribute to the regulatory genetic mechanisms that underlie higher neural activity, especially in learning and memory processes. However, the epigenetic regulation of gene expression in neurons remains insufficiently understood.
Mutations in complex subunits result in the development of pathologies. For instance, ARID1A and ARID1B subunit mutations in humans cause Coffin–Siris syndrome, which is a rare congenital multisystem genetic disease primarily characterized by developmental disabilities and intellectual disability. Currently, there are challenges in creating model systems to study Coffin–Siris syndrome. Drosophila has shown promise as a model organism due to its extensive research and suitability in studying neurodevelopmental pathologies. It is a cost-effective species that facilitates tracking of both species-specific features and general patterns for abnormality types. Additionally, Drosophila serves as a model organism due to its abundance of orthologous genes that lead to neuronal developmental abnormalities in humans. Notably, the knockdown of genes that encode subunit complexes in Drosophila produces a noticeable decline in long-term memory formation.
In this study, we examine the involvement of SAYP and osa complex subunits in different molecular mechanisms in Drosophila brain neurons. We use multiple strategies to alter the levels of SAYP and osa factors, such as tissue-specific knockdown, tissue-specific protein degradation, and null allele production. Using the CRISPR/Cas9 technique, we generated novel alleles of the osa and SAYP genes that encode operational proteins which can be selectively degraded at specific times and in specific tissues. We examine the changes in gene expression profiles, chromatin states, and the participation of transcription factors on chromatin, as well as DNA integrity alterations, upon removal of these factors from neurons. We are conducting research on the long-term memory of adult flies and neurogenesis at different developmental stages. Our aim is to gain insight into the role of the epigenetic regulator SWI/SNF in the development of nervous system pathologies and its involvement in the development and functioning of higher eukaryotic nervous systems.
ADDITIONAL INFORMATION
Funding sources. The study was supported by the RSF grant No. 20-14-00201.
Authors' contribution. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, and final approval of the version to be published and agree to be accountable for all aspects of the work.
Competing interests. The authors declare that they have no competing interests.
About the authors
R. V. Deev
Institute of Gene Biology of the Russian Academy of Sciences
Email: yul.biogen@yandex.ru
Russian Federation, Moscow
V. K. Chmykhalo
Institute of Gene Biology of the Russian Academy of Sciences
Email: yul.biogen@yandex.ru
Russian Federation, Moscow
N. G. Stepanov
Institute of Gene Biology of the Russian Academy of Sciences; I.M. Sechenov First Moscow State Medical University (Sechenov University)
Email: yul.biogen@yandex.ru
Russian Federation, Moscow; Moscow
L. A. Lebedeva
Institute of Gene Biology of the Russian Academy of Sciences
Email: yul.biogen@yandex.ru
Russian Federation, Moscow
Yu. V. Shidlovskii
Institute of Gene Biology of the Russian Academy of Sciences; I.M. Sechenov First Moscow State Medical University (Sechenov University)
Author for correspondence.
Email: yul.biogen@yandex.ru
Russian Federation, Moscow; Moscow
References
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