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RUNX1 induces DNA replication independent of active DNA demethylation at SPI1 regulatory regions

BACKGROUND: SPI1 is an essential transcription factor (TF) for the hematopoietic lineage, in which its expression is tightly controlled through a −17-kb upstream regulatory region and a promoter region. Both regulatory regions are demethylated during hematopoietic development, although how the chang...

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Autores principales: Goyal, Shubham, Suzuki, Takahiro, Li, Jing-Ru, Maeda, Shiori, Kishima, Mami, Nishimura, Hajime, Shimizu, Yuri, Suzuki, Harukazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381148/
https://www.ncbi.nlm.nih.gov/pubmed/28376714
http://dx.doi.org/10.1186/s12867-017-0087-y
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author Goyal, Shubham
Suzuki, Takahiro
Li, Jing-Ru
Maeda, Shiori
Kishima, Mami
Nishimura, Hajime
Shimizu, Yuri
Suzuki, Harukazu
author_facet Goyal, Shubham
Suzuki, Takahiro
Li, Jing-Ru
Maeda, Shiori
Kishima, Mami
Nishimura, Hajime
Shimizu, Yuri
Suzuki, Harukazu
author_sort Goyal, Shubham
collection PubMed
description BACKGROUND: SPI1 is an essential transcription factor (TF) for the hematopoietic lineage, in which its expression is tightly controlled through a −17-kb upstream regulatory region and a promoter region. Both regulatory regions are demethylated during hematopoietic development, although how the change of DNA methylation status is performed is still unknown. RESULTS: We found that the ectopic overexpression of RUNX1 (another key TF in hematopoiesis) in HEK-293T cells induces almost complete DNA demethylation at the −17-kb upstream regulatory region and partial but significant DNA demethylation at the proximal promoter region. This DNA demethylation occurred in mitomycin-C-treated nonproliferating cells at both regulatory regions, suggesting active DNA demethylation. Furthermore, ectopic RUNX1 expression induced significant endogenous SPI1 expression, although its expression level was much lower than that of natively SPI1-expressing monocyte cells. CONCLUSIONS: These results suggest the novel role of RUNX1 as an inducer of DNA demethylation at the SPI1 regulatory regions, although the mechanism of RUNX1-induced DNA demethylation remains to be explored.
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spelling pubmed-53811482017-04-10 RUNX1 induces DNA replication independent of active DNA demethylation at SPI1 regulatory regions Goyal, Shubham Suzuki, Takahiro Li, Jing-Ru Maeda, Shiori Kishima, Mami Nishimura, Hajime Shimizu, Yuri Suzuki, Harukazu BMC Mol Biol Research Article BACKGROUND: SPI1 is an essential transcription factor (TF) for the hematopoietic lineage, in which its expression is tightly controlled through a −17-kb upstream regulatory region and a promoter region. Both regulatory regions are demethylated during hematopoietic development, although how the change of DNA methylation status is performed is still unknown. RESULTS: We found that the ectopic overexpression of RUNX1 (another key TF in hematopoiesis) in HEK-293T cells induces almost complete DNA demethylation at the −17-kb upstream regulatory region and partial but significant DNA demethylation at the proximal promoter region. This DNA demethylation occurred in mitomycin-C-treated nonproliferating cells at both regulatory regions, suggesting active DNA demethylation. Furthermore, ectopic RUNX1 expression induced significant endogenous SPI1 expression, although its expression level was much lower than that of natively SPI1-expressing monocyte cells. CONCLUSIONS: These results suggest the novel role of RUNX1 as an inducer of DNA demethylation at the SPI1 regulatory regions, although the mechanism of RUNX1-induced DNA demethylation remains to be explored. BioMed Central 2017-04-04 /pmc/articles/PMC5381148/ /pubmed/28376714 http://dx.doi.org/10.1186/s12867-017-0087-y Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Goyal, Shubham
Suzuki, Takahiro
Li, Jing-Ru
Maeda, Shiori
Kishima, Mami
Nishimura, Hajime
Shimizu, Yuri
Suzuki, Harukazu
RUNX1 induces DNA replication independent of active DNA demethylation at SPI1 regulatory regions
title RUNX1 induces DNA replication independent of active DNA demethylation at SPI1 regulatory regions
title_full RUNX1 induces DNA replication independent of active DNA demethylation at SPI1 regulatory regions
title_fullStr RUNX1 induces DNA replication independent of active DNA demethylation at SPI1 regulatory regions
title_full_unstemmed RUNX1 induces DNA replication independent of active DNA demethylation at SPI1 regulatory regions
title_short RUNX1 induces DNA replication independent of active DNA demethylation at SPI1 regulatory regions
title_sort runx1 induces dna replication independent of active dna demethylation at spi1 regulatory regions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381148/
https://www.ncbi.nlm.nih.gov/pubmed/28376714
http://dx.doi.org/10.1186/s12867-017-0087-y
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