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The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells

Methylation of DNA at carbon 5 of cytosine is essential for mammalian development and implicated in transcriptional repression of genes and transposons. New patterns of DNA methylation characteristic of lineage-committed cells are established at the exit from pluripotency by de novo DNA methyltransf...

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Autores principales: Termanis, Ausma, Torrea, Natalia, Culley, Jayne, Kerr, Alastair, Ramsahoye, Bernard, Stancheva, Irina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027476/
https://www.ncbi.nlm.nih.gov/pubmed/27179028
http://dx.doi.org/10.1093/nar/gkw424
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author Termanis, Ausma
Torrea, Natalia
Culley, Jayne
Kerr, Alastair
Ramsahoye, Bernard
Stancheva, Irina
author_facet Termanis, Ausma
Torrea, Natalia
Culley, Jayne
Kerr, Alastair
Ramsahoye, Bernard
Stancheva, Irina
author_sort Termanis, Ausma
collection PubMed
description Methylation of DNA at carbon 5 of cytosine is essential for mammalian development and implicated in transcriptional repression of genes and transposons. New patterns of DNA methylation characteristic of lineage-committed cells are established at the exit from pluripotency by de novo DNA methyltransferases enzymes, DNMT3A and DNMT3B, which are regulated by developmental signaling and require access to chromatin-organized DNA. Whether or not the capacity for de novo DNA methylation of developmentally regulated loci is preserved in differentiated somatic cells and can occur in the absence of exogenous signals is currently unknown. Here, we demonstrate that fibroblasts derived from chromatin remodeling ATPase LSH (HELLS)-null mouse embryos, which lack DNA methylation from centromeric repeats, transposons and a number of gene promoters, are capable of reestablishing DNA methylation and silencing of misregulated genes upon re-expression of LSH. We also show that the ability of LSH to bind ATP and the cellular concentration of DNMT3B are critical for cell-autonomous de novo DNA methylation in somatic cells. These data suggest the existence of cellular memory that persists in differentiated cells through many cell generations and changes in transcriptional state.
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spelling pubmed-50274762016-09-21 The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells Termanis, Ausma Torrea, Natalia Culley, Jayne Kerr, Alastair Ramsahoye, Bernard Stancheva, Irina Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Methylation of DNA at carbon 5 of cytosine is essential for mammalian development and implicated in transcriptional repression of genes and transposons. New patterns of DNA methylation characteristic of lineage-committed cells are established at the exit from pluripotency by de novo DNA methyltransferases enzymes, DNMT3A and DNMT3B, which are regulated by developmental signaling and require access to chromatin-organized DNA. Whether or not the capacity for de novo DNA methylation of developmentally regulated loci is preserved in differentiated somatic cells and can occur in the absence of exogenous signals is currently unknown. Here, we demonstrate that fibroblasts derived from chromatin remodeling ATPase LSH (HELLS)-null mouse embryos, which lack DNA methylation from centromeric repeats, transposons and a number of gene promoters, are capable of reestablishing DNA methylation and silencing of misregulated genes upon re-expression of LSH. We also show that the ability of LSH to bind ATP and the cellular concentration of DNMT3B are critical for cell-autonomous de novo DNA methylation in somatic cells. These data suggest the existence of cellular memory that persists in differentiated cells through many cell generations and changes in transcriptional state. Oxford University Press 2016-09-19 2016-05-13 /pmc/articles/PMC5027476/ /pubmed/27179028 http://dx.doi.org/10.1093/nar/gkw424 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Termanis, Ausma
Torrea, Natalia
Culley, Jayne
Kerr, Alastair
Ramsahoye, Bernard
Stancheva, Irina
The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells
title The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells
title_full The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells
title_fullStr The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells
title_full_unstemmed The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells
title_short The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells
title_sort snf2 family atpase lsh promotes cell-autonomous de novo dna methylation in somatic cells
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027476/
https://www.ncbi.nlm.nih.gov/pubmed/27179028
http://dx.doi.org/10.1093/nar/gkw424
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