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Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan
Our previous work identified one region upstream human UGT2B4 (UDP glucuronosyltransferase family 2 member B4) which is associated with breast cancer and under balancing selection. However, the distribution, functional variation and molecular mechanism underlying breast cancer and balancing selectio...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950360/ https://www.ncbi.nlm.nih.gov/pubmed/36823244 http://dx.doi.org/10.1038/s41598-023-29682-x |
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author | Wang, Pin-Yi Yang, Yuan Shi, Xiao-Qian Chen, Ying Liu, Shao-Dong Wang, Hong-Yan Peng, Tao Shi, Qiang Zhang, Wei Sun, Chang |
author_facet | Wang, Pin-Yi Yang, Yuan Shi, Xiao-Qian Chen, Ying Liu, Shao-Dong Wang, Hong-Yan Peng, Tao Shi, Qiang Zhang, Wei Sun, Chang |
author_sort | Wang, Pin-Yi |
collection | PubMed |
description | Our previous work identified one region upstream human UGT2B4 (UDP glucuronosyltransferase family 2 member B4) which is associated with breast cancer and under balancing selection. However, the distribution, functional variation and molecular mechanism underlying breast cancer and balancing selection remain unclear. In current study, the two haplotypes with deep divergence are described by analyzing 1000 genomes project data and observed to be with high frequencies in all human populations. Through population genetics analysis and genome annotation, the potential functional region is identified and verified by reporter gene assay. Further mutagenesis indicates that the functional mutations are rs66862535 and rs68096061. Both SNPs can alter the interaction efficiency of transcription factor POU2F1 (POU class 2 homeobox 1). Through chromosome conformation capture, it is identified that the enhancer containing these two SNPs can interact with UGT2B4 promoter. Expression quantitative trait loci analysis indicates that UGT2B4 expression is dependent on the genotype of this locus. The common haplotype in human is lost in four genomes of archaic hominins, which suggests that Neanderthal and Denisovan should present relatively lower UGT2B4 expression and further higher steroid hormone level. This study provides new insight into the contribution of ancient population structure to human phenotypes. |
format | Online Article Text |
id | pubmed-9950360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99503602023-02-25 Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan Wang, Pin-Yi Yang, Yuan Shi, Xiao-Qian Chen, Ying Liu, Shao-Dong Wang, Hong-Yan Peng, Tao Shi, Qiang Zhang, Wei Sun, Chang Sci Rep Article Our previous work identified one region upstream human UGT2B4 (UDP glucuronosyltransferase family 2 member B4) which is associated with breast cancer and under balancing selection. However, the distribution, functional variation and molecular mechanism underlying breast cancer and balancing selection remain unclear. In current study, the two haplotypes with deep divergence are described by analyzing 1000 genomes project data and observed to be with high frequencies in all human populations. Through population genetics analysis and genome annotation, the potential functional region is identified and verified by reporter gene assay. Further mutagenesis indicates that the functional mutations are rs66862535 and rs68096061. Both SNPs can alter the interaction efficiency of transcription factor POU2F1 (POU class 2 homeobox 1). Through chromosome conformation capture, it is identified that the enhancer containing these two SNPs can interact with UGT2B4 promoter. Expression quantitative trait loci analysis indicates that UGT2B4 expression is dependent on the genotype of this locus. The common haplotype in human is lost in four genomes of archaic hominins, which suggests that Neanderthal and Denisovan should present relatively lower UGT2B4 expression and further higher steroid hormone level. This study provides new insight into the contribution of ancient population structure to human phenotypes. Nature Publishing Group UK 2023-02-23 /pmc/articles/PMC9950360/ /pubmed/36823244 http://dx.doi.org/10.1038/s41598-023-29682-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Pin-Yi Yang, Yuan Shi, Xiao-Qian Chen, Ying Liu, Shao-Dong Wang, Hong-Yan Peng, Tao Shi, Qiang Zhang, Wei Sun, Chang Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan |
title | Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan |
title_full | Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan |
title_fullStr | Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan |
title_full_unstemmed | Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan |
title_short | Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan |
title_sort | distilling functional variations for human ugt2b4 upstream region based on selection signals and implications for phenotypes of neanderthal and denisovan |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950360/ https://www.ncbi.nlm.nih.gov/pubmed/36823244 http://dx.doi.org/10.1038/s41598-023-29682-x |
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