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Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle

BACKGROUND: Causal variants for complex traits, such as eQTL are often found in non-coding regions of the genome, where they are hypothesised to influence phenotypes by regulating gene expression. Many regulatory regions are marked by histone modifications, which can be assayed by chromatin immunopr...

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Autores principales: Prowse-Wilkins, Claire P., Lopdell, Thomas J., Xiang, Ruidong, Vander Jagt, Christy J., Littlejohn, Mathew D., Chamberlain, Amanda J., Goddard, Michael E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9733386/
https://www.ncbi.nlm.nih.gov/pubmed/36482302
http://dx.doi.org/10.1186/s12864-022-09002-9
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author Prowse-Wilkins, Claire P.
Lopdell, Thomas J.
Xiang, Ruidong
Vander Jagt, Christy J.
Littlejohn, Mathew D.
Chamberlain, Amanda J.
Goddard, Michael E.
author_facet Prowse-Wilkins, Claire P.
Lopdell, Thomas J.
Xiang, Ruidong
Vander Jagt, Christy J.
Littlejohn, Mathew D.
Chamberlain, Amanda J.
Goddard, Michael E.
author_sort Prowse-Wilkins, Claire P.
collection PubMed
description BACKGROUND: Causal variants for complex traits, such as eQTL are often found in non-coding regions of the genome, where they are hypothesised to influence phenotypes by regulating gene expression. Many regulatory regions are marked by histone modifications, which can be assayed by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Sequence reads from ChIP-seq form peaks at putative regulatory regions, which may reflect the amount of regulatory activity at this region. Therefore, eQTL which are also associated with differences in histone modifications are excellent candidate causal variants. RESULTS: We assayed the histone modifications H3K4Me3, H3K4Me1 and H3K27ac and mRNA in the mammary gland of up to 400 animals. We identified QTL for peak height (histone QTL), exon expression (eeQTL), allele specific expression (aseQTL) and allele specific binding (asbQTL). By intersecting these results, we identify variants which may influence gene expression by altering regulatory regions of the genome, and may be causal variants for other traits. Lastly, we find that these variants are found in putative transcription factor binding sites, identifying a mechanism for the effect of many eQTL. CONCLUSIONS: We find that allele specific and traditional QTL analysis often identify the same genetic variants and provide evidence that many eQTL are regulatory variants which alter activity at regulatory regions of the bovine genome. Our work provides methodological and biological updates on how regulatory mechanisms interplay at multi-omics levels. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-09002-9.
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spelling pubmed-97333862022-12-10 Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle Prowse-Wilkins, Claire P. Lopdell, Thomas J. Xiang, Ruidong Vander Jagt, Christy J. Littlejohn, Mathew D. Chamberlain, Amanda J. Goddard, Michael E. BMC Genomics Research BACKGROUND: Causal variants for complex traits, such as eQTL are often found in non-coding regions of the genome, where they are hypothesised to influence phenotypes by regulating gene expression. Many regulatory regions are marked by histone modifications, which can be assayed by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Sequence reads from ChIP-seq form peaks at putative regulatory regions, which may reflect the amount of regulatory activity at this region. Therefore, eQTL which are also associated with differences in histone modifications are excellent candidate causal variants. RESULTS: We assayed the histone modifications H3K4Me3, H3K4Me1 and H3K27ac and mRNA in the mammary gland of up to 400 animals. We identified QTL for peak height (histone QTL), exon expression (eeQTL), allele specific expression (aseQTL) and allele specific binding (asbQTL). By intersecting these results, we identify variants which may influence gene expression by altering regulatory regions of the genome, and may be causal variants for other traits. Lastly, we find that these variants are found in putative transcription factor binding sites, identifying a mechanism for the effect of many eQTL. CONCLUSIONS: We find that allele specific and traditional QTL analysis often identify the same genetic variants and provide evidence that many eQTL are regulatory variants which alter activity at regulatory regions of the bovine genome. Our work provides methodological and biological updates on how regulatory mechanisms interplay at multi-omics levels. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-09002-9. BioMed Central 2022-12-08 /pmc/articles/PMC9733386/ /pubmed/36482302 http://dx.doi.org/10.1186/s12864-022-09002-9 Text en © Crown 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Prowse-Wilkins, Claire P.
Lopdell, Thomas J.
Xiang, Ruidong
Vander Jagt, Christy J.
Littlejohn, Mathew D.
Chamberlain, Amanda J.
Goddard, Michael E.
Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle
title Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle
title_full Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle
title_fullStr Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle
title_full_unstemmed Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle
title_short Genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle
title_sort genetic variation in histone modifications and gene expression identifies regulatory variants in the mammary gland of cattle
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9733386/
https://www.ncbi.nlm.nih.gov/pubmed/36482302
http://dx.doi.org/10.1186/s12864-022-09002-9
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