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Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription

The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand...

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Autores principales: Xie, Qiu, Li, Caihua, Song, Xiaozhen, Wu, Lihua, Jiang, Qian, Qiu, Zhiyong, Cao, Haiyan, Yu, Kaihui, Wan, Chunlei, Li, Jianting, Yang, Feng, Huang, Zebing, niu, Bo, Jiang, Zhengwen, Zhang, Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389733/
https://www.ncbi.nlm.nih.gov/pubmed/27924000
http://dx.doi.org/10.1093/nar/gkw1208
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author Xie, Qiu
Li, Caihua
Song, Xiaozhen
Wu, Lihua
Jiang, Qian
Qiu, Zhiyong
Cao, Haiyan
Yu, Kaihui
Wan, Chunlei
Li, Jianting
Yang, Feng
Huang, Zebing
niu, Bo
Jiang, Zhengwen
Zhang, Ting
author_facet Xie, Qiu
Li, Caihua
Song, Xiaozhen
Wu, Lihua
Jiang, Qian
Qiu, Zhiyong
Cao, Haiyan
Yu, Kaihui
Wan, Chunlei
Li, Jianting
Yang, Feng
Huang, Zebing
niu, Bo
Jiang, Zhengwen
Zhang, Ting
author_sort Xie, Qiu
collection PubMed
description The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark. Enrichment H3K4me1 at the hot spots of DSB regions enhanced the recruitment of upstream binding factor (UBF) to rRNA genes, resulting in the increment of rRNA genes transcription. Supplement of folate resulted in a restored UBF binding across DNA breakage sites of rRNA genes, and normal rRNA gene transcription. In samples from neural tube defects (NTDs) with low folate level, up-regulation of rRNA gene transcription was observed, along with aberrant UBF level. Our results present a new view by which alterations in folate levels affects DNA breakage through epigenetic control leading to the regulation of rRNA gene transcription during the early stage of development.
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spelling pubmed-53897332017-04-24 Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription Xie, Qiu Li, Caihua Song, Xiaozhen Wu, Lihua Jiang, Qian Qiu, Zhiyong Cao, Haiyan Yu, Kaihui Wan, Chunlei Li, Jianting Yang, Feng Huang, Zebing niu, Bo Jiang, Zhengwen Zhang, Ting Nucleic Acids Res Gene regulation, Chromatin and Epigenetics The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark. Enrichment H3K4me1 at the hot spots of DSB regions enhanced the recruitment of upstream binding factor (UBF) to rRNA genes, resulting in the increment of rRNA genes transcription. Supplement of folate resulted in a restored UBF binding across DNA breakage sites of rRNA genes, and normal rRNA gene transcription. In samples from neural tube defects (NTDs) with low folate level, up-regulation of rRNA gene transcription was observed, along with aberrant UBF level. Our results present a new view by which alterations in folate levels affects DNA breakage through epigenetic control leading to the regulation of rRNA gene transcription during the early stage of development. Oxford University Press 2017-03-17 2016-12-06 /pmc/articles/PMC5389733/ /pubmed/27924000 http://dx.doi.org/10.1093/nar/gkw1208 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Xie, Qiu
Li, Caihua
Song, Xiaozhen
Wu, Lihua
Jiang, Qian
Qiu, Zhiyong
Cao, Haiyan
Yu, Kaihui
Wan, Chunlei
Li, Jianting
Yang, Feng
Huang, Zebing
niu, Bo
Jiang, Zhengwen
Zhang, Ting
Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription
title Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription
title_full Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription
title_fullStr Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription
title_full_unstemmed Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription
title_short Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription
title_sort folate deficiency facilitates recruitment of upstream binding factor to hot spots of dna double-strand breaks of rrna genes and promotes its transcription
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389733/
https://www.ncbi.nlm.nih.gov/pubmed/27924000
http://dx.doi.org/10.1093/nar/gkw1208
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