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Large conserved domains of low DNA methylation maintained by Dnmt3a

Gains and losses in DNA methylation are prominent features of mammalian cell types. To gain insight into mechanisms that could promote shifts in DNA methylation and contribute to cell fate changes, including malignant transformation, we performed genome-wide mapping of 5-methylcytosine and 5-hydroxy...

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Autores principales: Jeong, Mira, Sun, Deqiang, Luo, Min, Huang, Yun, Challen, Grant A., Rodriguez, Benjamin, Zhang, Xiaotian, Chavez, Lukas, Wang, Hui, Hannah, Rebecca, Kim, Sang-Bae, Yang, Liubin, Ko, Myunggon, Chen, Rui, Göttgens, Berthold, Lee, Ju-Seog, Gunaratne, Preethi, Godley, Lucy A., Darlington, Gretchen J., Rao, Anjana, Li, Wei, Goodell, Margaret A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920905/
https://www.ncbi.nlm.nih.gov/pubmed/24270360
http://dx.doi.org/10.1038/ng.2836
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author Jeong, Mira
Sun, Deqiang
Luo, Min
Huang, Yun
Challen, Grant A.
Rodriguez, Benjamin
Zhang, Xiaotian
Chavez, Lukas
Wang, Hui
Hannah, Rebecca
Kim, Sang-Bae
Yang, Liubin
Ko, Myunggon
Chen, Rui
Göttgens, Berthold
Lee, Ju-Seog
Gunaratne, Preethi
Godley, Lucy A.
Darlington, Gretchen J.
Rao, Anjana
Li, Wei
Goodell, Margaret A.
author_facet Jeong, Mira
Sun, Deqiang
Luo, Min
Huang, Yun
Challen, Grant A.
Rodriguez, Benjamin
Zhang, Xiaotian
Chavez, Lukas
Wang, Hui
Hannah, Rebecca
Kim, Sang-Bae
Yang, Liubin
Ko, Myunggon
Chen, Rui
Göttgens, Berthold
Lee, Ju-Seog
Gunaratne, Preethi
Godley, Lucy A.
Darlington, Gretchen J.
Rao, Anjana
Li, Wei
Goodell, Margaret A.
author_sort Jeong, Mira
collection PubMed
description Gains and losses in DNA methylation are prominent features of mammalian cell types. To gain insight into mechanisms that could promote shifts in DNA methylation and contribute to cell fate changes, including malignant transformation, we performed genome-wide mapping of 5-methylcytosine and 5-hydroxymethylcytosine in purified murine hematopoietic stem cells. We discovered extended regions of low methylation (Canyons) that span conserved domains frequently containing transcription factors and are distinct from CpG islands and shores. The genes in about half of these methylation Canyons are coated with repressive histone marks while the remainder are covered by activating histone marks and are highly expressed in HSCs. Canyon borders are demarked by 5-hydroxymethylcytosine and become eroded in the absence of DNA methyltransferase 3a (Dnmt3a). Genes dysregulated in human leukemias are enriched for Canyon-associated genes. The novel epigenetic landscape we describe may provide a mechanism for the regulation of hematopoiesis and may contribute to leukemia development.
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spelling pubmed-39209052014-07-01 Large conserved domains of low DNA methylation maintained by Dnmt3a Jeong, Mira Sun, Deqiang Luo, Min Huang, Yun Challen, Grant A. Rodriguez, Benjamin Zhang, Xiaotian Chavez, Lukas Wang, Hui Hannah, Rebecca Kim, Sang-Bae Yang, Liubin Ko, Myunggon Chen, Rui Göttgens, Berthold Lee, Ju-Seog Gunaratne, Preethi Godley, Lucy A. Darlington, Gretchen J. Rao, Anjana Li, Wei Goodell, Margaret A. Nat Genet Article Gains and losses in DNA methylation are prominent features of mammalian cell types. To gain insight into mechanisms that could promote shifts in DNA methylation and contribute to cell fate changes, including malignant transformation, we performed genome-wide mapping of 5-methylcytosine and 5-hydroxymethylcytosine in purified murine hematopoietic stem cells. We discovered extended regions of low methylation (Canyons) that span conserved domains frequently containing transcription factors and are distinct from CpG islands and shores. The genes in about half of these methylation Canyons are coated with repressive histone marks while the remainder are covered by activating histone marks and are highly expressed in HSCs. Canyon borders are demarked by 5-hydroxymethylcytosine and become eroded in the absence of DNA methyltransferase 3a (Dnmt3a). Genes dysregulated in human leukemias are enriched for Canyon-associated genes. The novel epigenetic landscape we describe may provide a mechanism for the regulation of hematopoiesis and may contribute to leukemia development. 2013-11-24 2014-01 /pmc/articles/PMC3920905/ /pubmed/24270360 http://dx.doi.org/10.1038/ng.2836 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Jeong, Mira
Sun, Deqiang
Luo, Min
Huang, Yun
Challen, Grant A.
Rodriguez, Benjamin
Zhang, Xiaotian
Chavez, Lukas
Wang, Hui
Hannah, Rebecca
Kim, Sang-Bae
Yang, Liubin
Ko, Myunggon
Chen, Rui
Göttgens, Berthold
Lee, Ju-Seog
Gunaratne, Preethi
Godley, Lucy A.
Darlington, Gretchen J.
Rao, Anjana
Li, Wei
Goodell, Margaret A.
Large conserved domains of low DNA methylation maintained by Dnmt3a
title Large conserved domains of low DNA methylation maintained by Dnmt3a
title_full Large conserved domains of low DNA methylation maintained by Dnmt3a
title_fullStr Large conserved domains of low DNA methylation maintained by Dnmt3a
title_full_unstemmed Large conserved domains of low DNA methylation maintained by Dnmt3a
title_short Large conserved domains of low DNA methylation maintained by Dnmt3a
title_sort large conserved domains of low dna methylation maintained by dnmt3a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920905/
https://www.ncbi.nlm.nih.gov/pubmed/24270360
http://dx.doi.org/10.1038/ng.2836
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