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Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis
Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. Previous studies focused on transcriptional regulation modulated by proximal upstream cis-regulatory elements (CREs) of the human vegfa promoter. However, we hypothesized that distal upstream CREs may also be involved in...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389716/ https://www.ncbi.nlm.nih.gov/pubmed/27913726 http://dx.doi.org/10.1093/nar/gkw1187 |
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author | Fu, Chuan-Yang Wang, Po-Chun Tsai, Huai-Jen |
author_facet | Fu, Chuan-Yang Wang, Po-Chun Tsai, Huai-Jen |
author_sort | Fu, Chuan-Yang |
collection | PubMed |
description | Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. Previous studies focused on transcriptional regulation modulated by proximal upstream cis-regulatory elements (CREs) of the human vegfa promoter. However, we hypothesized that distal upstream CREs may also be involved in controlling vegfa transcription. In this study, we found that the catalytic domain of Seryl-tRNA synthetase (SerRS) interacted with transcription factor Yin Yang 1 (YY1) to form a SerRS/YY1 complex that negatively controls vegfa promoter activity through binding distal CREs at −4654 to −4623 of vegfa. Particularly, we demonstrated that the −4654 to −4623 segment, which predominantly controls vegfa promoter activity, is involved in competitive binding between SerRS/YY1 complex and NFKB1. We further showed that VEGFA protein and blood vessel development were reduced by overexpression of either SerRS or YY1, but enhanced by the knockdown of either SerRS or yy1. In contrast, these same parameters were enhanced by overexpression of NFKB1, but reduced by knockdown of nfkb1. Therefore, we suggested that SerRS does not bind DNA directly but form a SerRS/YY1 complex, which functions as a negative effector to regulate vegfa transcription through binding at the distal CREs; while NFKB1 serves as a positive effector through competing with SerRS/YY1 binding at the overlapping CREs. |
format | Online Article Text |
id | pubmed-5389716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53897162017-04-24 Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis Fu, Chuan-Yang Wang, Po-Chun Tsai, Huai-Jen Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. Previous studies focused on transcriptional regulation modulated by proximal upstream cis-regulatory elements (CREs) of the human vegfa promoter. However, we hypothesized that distal upstream CREs may also be involved in controlling vegfa transcription. In this study, we found that the catalytic domain of Seryl-tRNA synthetase (SerRS) interacted with transcription factor Yin Yang 1 (YY1) to form a SerRS/YY1 complex that negatively controls vegfa promoter activity through binding distal CREs at −4654 to −4623 of vegfa. Particularly, we demonstrated that the −4654 to −4623 segment, which predominantly controls vegfa promoter activity, is involved in competitive binding between SerRS/YY1 complex and NFKB1. We further showed that VEGFA protein and blood vessel development were reduced by overexpression of either SerRS or YY1, but enhanced by the knockdown of either SerRS or yy1. In contrast, these same parameters were enhanced by overexpression of NFKB1, but reduced by knockdown of nfkb1. Therefore, we suggested that SerRS does not bind DNA directly but form a SerRS/YY1 complex, which functions as a negative effector to regulate vegfa transcription through binding at the distal CREs; while NFKB1 serves as a positive effector through competing with SerRS/YY1 binding at the overlapping CREs. Oxford University Press 2017-03-17 2016-11-29 /pmc/articles/PMC5389716/ /pubmed/27913726 http://dx.doi.org/10.1093/nar/gkw1187 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 Fu, Chuan-Yang Wang, Po-Chun Tsai, Huai-Jen Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis |
title | Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis |
title_full | Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis |
title_fullStr | Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis |
title_full_unstemmed | Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis |
title_short | Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis |
title_sort | competitive binding between seryl-trna synthetase/yy1 complex and nfkb1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389716/ https://www.ncbi.nlm.nih.gov/pubmed/27913726 http://dx.doi.org/10.1093/nar/gkw1187 |
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