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Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity
Myocardin-related transcription factor A (MRTF-A), a coactivator of serum response factor (SRF), regulates the expression of many cytoskeletal genes in response to cytoplasmic and nuclear actin dynamics. Here we describe a novel mechanism to regulate MRTF-A activity within the nucleus by showing tha...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831594/ https://www.ncbi.nlm.nih.gov/pubmed/35145145 http://dx.doi.org/10.1038/s41598-022-06135-5 |
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author | Sidorenko, Ekaterina Sokolova, Maria Pennanen, Antti P. Kyheröinen, Salla Posern, Guido Foisner, Roland Vartiainen, Maria K. |
author_facet | Sidorenko, Ekaterina Sokolova, Maria Pennanen, Antti P. Kyheröinen, Salla Posern, Guido Foisner, Roland Vartiainen, Maria K. |
author_sort | Sidorenko, Ekaterina |
collection | PubMed |
description | Myocardin-related transcription factor A (MRTF-A), a coactivator of serum response factor (SRF), regulates the expression of many cytoskeletal genes in response to cytoplasmic and nuclear actin dynamics. Here we describe a novel mechanism to regulate MRTF-A activity within the nucleus by showing that lamina-associated polypeptide 2α (Lap2α), the nucleoplasmic isoform of Lap2, is a direct binding partner of MRTF-A, and required for the efficient expression of MRTF-A/SRF target genes. Mechanistically, Lap2α is not required for MRTF-A nuclear localization, unlike most other MRTF-A regulators, but is required for efficient recruitment of MRTF-A to its target genes. This regulatory step takes place prior to MRTF-A chromatin binding, because Lap2α neither interacts with, nor specifically influences active histone marks on MRTF-A/SRF target genes. Phenotypically, Lap2α is required for serum-induced cell migration, and deregulated MRTF-A activity may also contribute to muscle and proliferation phenotypes associated with loss of Lap2α. Our studies therefore add another regulatory layer to the control of MRTF-A-SRF-mediated gene expression, and broaden the role of Lap2α in transcriptional regulation. |
format | Online Article Text |
id | pubmed-8831594 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-88315942022-02-14 Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity Sidorenko, Ekaterina Sokolova, Maria Pennanen, Antti P. Kyheröinen, Salla Posern, Guido Foisner, Roland Vartiainen, Maria K. Sci Rep Article Myocardin-related transcription factor A (MRTF-A), a coactivator of serum response factor (SRF), regulates the expression of many cytoskeletal genes in response to cytoplasmic and nuclear actin dynamics. Here we describe a novel mechanism to regulate MRTF-A activity within the nucleus by showing that lamina-associated polypeptide 2α (Lap2α), the nucleoplasmic isoform of Lap2, is a direct binding partner of MRTF-A, and required for the efficient expression of MRTF-A/SRF target genes. Mechanistically, Lap2α is not required for MRTF-A nuclear localization, unlike most other MRTF-A regulators, but is required for efficient recruitment of MRTF-A to its target genes. This regulatory step takes place prior to MRTF-A chromatin binding, because Lap2α neither interacts with, nor specifically influences active histone marks on MRTF-A/SRF target genes. Phenotypically, Lap2α is required for serum-induced cell migration, and deregulated MRTF-A activity may also contribute to muscle and proliferation phenotypes associated with loss of Lap2α. Our studies therefore add another regulatory layer to the control of MRTF-A-SRF-mediated gene expression, and broaden the role of Lap2α in transcriptional regulation. Nature Publishing Group UK 2022-02-10 /pmc/articles/PMC8831594/ /pubmed/35145145 http://dx.doi.org/10.1038/s41598-022-06135-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sidorenko, Ekaterina Sokolova, Maria Pennanen, Antti P. Kyheröinen, Salla Posern, Guido Foisner, Roland Vartiainen, Maria K. Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity |
title | Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity |
title_full | Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity |
title_fullStr | Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity |
title_full_unstemmed | Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity |
title_short | Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity |
title_sort | lamina-associated polypeptide 2α is required for intranuclear mrtf-a activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831594/ https://www.ncbi.nlm.nih.gov/pubmed/35145145 http://dx.doi.org/10.1038/s41598-022-06135-5 |
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