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Methylation of a CGATA element inhibits binding and regulation by GATA-1
Alterations in DNA methylation occur during development, but the mechanisms by which they influence gene expression remain uncertain. There are few examples where modification of a single CpG dinucleotide directly affects transcription factor binding and regulation of a target gene in vivo. Here, we...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244756/ https://www.ncbi.nlm.nih.gov/pubmed/32444652 http://dx.doi.org/10.1038/s41467-020-16388-1 |
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author | Yang, Lu Chen, Zhiliang Stout, Elizabeth S. Delerue, Fabien Ittner, Lars M. Wilkins, Marc R. Quinlan, Kate G. R. Crossley, Merlin |
author_facet | Yang, Lu Chen, Zhiliang Stout, Elizabeth S. Delerue, Fabien Ittner, Lars M. Wilkins, Marc R. Quinlan, Kate G. R. Crossley, Merlin |
author_sort | Yang, Lu |
collection | PubMed |
description | Alterations in DNA methylation occur during development, but the mechanisms by which they influence gene expression remain uncertain. There are few examples where modification of a single CpG dinucleotide directly affects transcription factor binding and regulation of a target gene in vivo. Here, we show that the erythroid transcription factor GATA-1 — that typically binds T/AGATA sites — can also recognise CGATA elements, but only if the CpG dinucleotide is unmethylated. We focus on a single CGATA site in the c-Kit gene which progressively becomes unmethylated during haematopoiesis. We observe that methylation attenuates GATA-1 binding and gene regulation in cell lines. In mice, converting the CGATA element to a TGATA site that cannot be methylated leads to accumulation of megakaryocyte-erythroid progenitors. Thus, the CpG dinucleotide is essential for normal erythropoiesis and this study illustrates how a single methylated CpG can directly affect transcription factor binding and cellular regulation. |
format | Online Article Text |
id | pubmed-7244756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72447562020-06-03 Methylation of a CGATA element inhibits binding and regulation by GATA-1 Yang, Lu Chen, Zhiliang Stout, Elizabeth S. Delerue, Fabien Ittner, Lars M. Wilkins, Marc R. Quinlan, Kate G. R. Crossley, Merlin Nat Commun Article Alterations in DNA methylation occur during development, but the mechanisms by which they influence gene expression remain uncertain. There are few examples where modification of a single CpG dinucleotide directly affects transcription factor binding and regulation of a target gene in vivo. Here, we show that the erythroid transcription factor GATA-1 — that typically binds T/AGATA sites — can also recognise CGATA elements, but only if the CpG dinucleotide is unmethylated. We focus on a single CGATA site in the c-Kit gene which progressively becomes unmethylated during haematopoiesis. We observe that methylation attenuates GATA-1 binding and gene regulation in cell lines. In mice, converting the CGATA element to a TGATA site that cannot be methylated leads to accumulation of megakaryocyte-erythroid progenitors. Thus, the CpG dinucleotide is essential for normal erythropoiesis and this study illustrates how a single methylated CpG can directly affect transcription factor binding and cellular regulation. Nature Publishing Group UK 2020-05-22 /pmc/articles/PMC7244756/ /pubmed/32444652 http://dx.doi.org/10.1038/s41467-020-16388-1 Text en © The Author(s) 2020 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yang, Lu Chen, Zhiliang Stout, Elizabeth S. Delerue, Fabien Ittner, Lars M. Wilkins, Marc R. Quinlan, Kate G. R. Crossley, Merlin Methylation of a CGATA element inhibits binding and regulation by GATA-1 |
title | Methylation of a CGATA element inhibits binding and regulation by GATA-1 |
title_full | Methylation of a CGATA element inhibits binding and regulation by GATA-1 |
title_fullStr | Methylation of a CGATA element inhibits binding and regulation by GATA-1 |
title_full_unstemmed | Methylation of a CGATA element inhibits binding and regulation by GATA-1 |
title_short | Methylation of a CGATA element inhibits binding and regulation by GATA-1 |
title_sort | methylation of a cgata element inhibits binding and regulation by gata-1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244756/ https://www.ncbi.nlm.nih.gov/pubmed/32444652 http://dx.doi.org/10.1038/s41467-020-16388-1 |
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