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Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts

Lymphoid specific helicase (Lsh) belongs to the family of SNF2/helicases. Disruption of Lsh leads to developmental growth retardation and premature aging in mice. However, the specific effect of Lsh on human cellular senescence remains unknown. Herein, we report that Lsh overexpression delays cell s...

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Detalles Bibliográficos
Autores principales: Zhou, Rui, Han, Limin, Li, Guodong, Tong, Tanjun
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731912/
https://www.ncbi.nlm.nih.gov/pubmed/19561196
http://dx.doi.org/10.1093/nar/gkp533
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author Zhou, Rui
Han, Limin
Li, Guodong
Tong, Tanjun
author_facet Zhou, Rui
Han, Limin
Li, Guodong
Tong, Tanjun
author_sort Zhou, Rui
collection PubMed
description Lymphoid specific helicase (Lsh) belongs to the family of SNF2/helicases. Disruption of Lsh leads to developmental growth retardation and premature aging in mice. However, the specific effect of Lsh on human cellular senescence remains unknown. Herein, we report that Lsh overexpression delays cell senescence by silencing p16(INK4a) in human fibroblasts. The patterns of p16(INK4a) and Lsh expression during cell senescence present the inverse correlation. We also find that Lsh requires histone deacetylase (HDAC) activity to repress p16(INK4a) and treatment with trichostatin A (TSA) is sufficient to block the repressor effect of Lsh. Moreover, overexpression of Lsh is correlated with deacetylation of histone H3 at the p16 promoter, and TSA treatment in Lsh-expressing cells reverses the acetylation status of histones. Additionally, we demonstrate an interaction between Lsh, histone deacetylase 1 (HDAC1) and HDAC2 in vivo. Furthermore, we demonstrate that Lsh interacts in vivo with the p16 promoter and recruits HDAC1. Our data suggest that Lsh represses endogenous p16(INK4a) expression by recruiting HDAC to establish a repressive chromatin structure at the p16(INK4a) promoter, which in turn delays cell senescence.
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spelling pubmed-27319122009-09-10 Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts Zhou, Rui Han, Limin Li, Guodong Tong, Tanjun Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics Lymphoid specific helicase (Lsh) belongs to the family of SNF2/helicases. Disruption of Lsh leads to developmental growth retardation and premature aging in mice. However, the specific effect of Lsh on human cellular senescence remains unknown. Herein, we report that Lsh overexpression delays cell senescence by silencing p16(INK4a) in human fibroblasts. The patterns of p16(INK4a) and Lsh expression during cell senescence present the inverse correlation. We also find that Lsh requires histone deacetylase (HDAC) activity to repress p16(INK4a) and treatment with trichostatin A (TSA) is sufficient to block the repressor effect of Lsh. Moreover, overexpression of Lsh is correlated with deacetylation of histone H3 at the p16 promoter, and TSA treatment in Lsh-expressing cells reverses the acetylation status of histones. Additionally, we demonstrate an interaction between Lsh, histone deacetylase 1 (HDAC1) and HDAC2 in vivo. Furthermore, we demonstrate that Lsh interacts in vivo with the p16 promoter and recruits HDAC1. Our data suggest that Lsh represses endogenous p16(INK4a) expression by recruiting HDAC to establish a repressive chromatin structure at the p16(INK4a) promoter, which in turn delays cell senescence. Oxford University Press 2009-08 2009-06-26 /pmc/articles/PMC2731912/ /pubmed/19561196 http://dx.doi.org/10.1093/nar/gkp533 Text en © 2009 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene Regulation, Chromatin and Epigenetics
Zhou, Rui
Han, Limin
Li, Guodong
Tong, Tanjun
Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts
title Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts
title_full Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts
title_fullStr Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts
title_full_unstemmed Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts
title_short Senescence delay and repression of p16(INK4a) by Lsh via recruitment of histone deacetylases in human diploid fibroblasts
title_sort senescence delay and repression of p16(ink4a) by lsh via recruitment of histone deacetylases in human diploid fibroblasts
topic Gene Regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731912/
https://www.ncbi.nlm.nih.gov/pubmed/19561196
http://dx.doi.org/10.1093/nar/gkp533
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