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Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck

Avian eggshell color is an interesting genetic trait. Here, we report that the blue eggshell color of the domestic duck is caused by two cis-regulatory G to A transitions upstream of ABCG2, which encodes an efflux transporter. The juxtaposed blue eggshell allele A-A exhibited higher promoter activit...

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Autores principales: Chen, Li, Gu, Xiaorong, Huang, Xuetao, Liu, Rui, Li, Jinxiu, Hu, Yiqing, Li, Guoqin, Zeng, Tao, Tian, Yong, Hu, Xiaoxiang, Lu, Lizhi, Li, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688135/
https://www.ncbi.nlm.nih.gov/pubmed/33186356
http://dx.doi.org/10.1371/journal.pgen.1009119
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author Chen, Li
Gu, Xiaorong
Huang, Xuetao
Liu, Rui
Li, Jinxiu
Hu, Yiqing
Li, Guoqin
Zeng, Tao
Tian, Yong
Hu, Xiaoxiang
Lu, Lizhi
Li, Ning
author_facet Chen, Li
Gu, Xiaorong
Huang, Xuetao
Liu, Rui
Li, Jinxiu
Hu, Yiqing
Li, Guoqin
Zeng, Tao
Tian, Yong
Hu, Xiaoxiang
Lu, Lizhi
Li, Ning
author_sort Chen, Li
collection PubMed
description Avian eggshell color is an interesting genetic trait. Here, we report that the blue eggshell color of the domestic duck is caused by two cis-regulatory G to A transitions upstream of ABCG2, which encodes an efflux transporter. The juxtaposed blue eggshell allele A-A exhibited higher promoter activity and stronger nuclear protein binding capacity than the white eggshell allele G-G. Transcription factor analysis suggested differential binding capability of CTCF between blue eggshell and white eggshell alleles. Knockdown of CTCF expression significantly decreased the promoter activity of the blue eggshell but not the white eggshell allele. DNA methylation analysis revealed similar high methylation of the region upstream of the CTCF binding sites in both blue-eggshelled and white-eggshelled ducks. However, DNA methylation levels downstream of the binding sites were decreased and 35% lower in blue-eggshelled ducks than in white-eggshelled ducks. Consistent with the in vitro regulatory pattern of causative sites, ABCG2 exhibited higher expression in uteruses of blue-eggshelled ducks and also showed polarized distribution in their endometrial epithelial cells, distributing at the apical surface of endometrial epithelial cells and with orientation toward the uterine cavity, where the eggshell is pigmented. In conclusion, our results suggest that two cis-regulatory SNPs upstream of ABCG2 are the causative mutations for blue eggshells in ducks. The blue eggshell variant up-regulated ABCG2 expression through recruiting CTCF binding, which may function as a barrier element to shield the downstream region from high methylation levels present upstream. ABCG2 was identified as the only candidate causative gene for blue eggshells; it may function as an efflux transporter of biliverdin to the uterine cavity.
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spelling pubmed-76881352020-12-05 Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck Chen, Li Gu, Xiaorong Huang, Xuetao Liu, Rui Li, Jinxiu Hu, Yiqing Li, Guoqin Zeng, Tao Tian, Yong Hu, Xiaoxiang Lu, Lizhi Li, Ning PLoS Genet Research Article Avian eggshell color is an interesting genetic trait. Here, we report that the blue eggshell color of the domestic duck is caused by two cis-regulatory G to A transitions upstream of ABCG2, which encodes an efflux transporter. The juxtaposed blue eggshell allele A-A exhibited higher promoter activity and stronger nuclear protein binding capacity than the white eggshell allele G-G. Transcription factor analysis suggested differential binding capability of CTCF between blue eggshell and white eggshell alleles. Knockdown of CTCF expression significantly decreased the promoter activity of the blue eggshell but not the white eggshell allele. DNA methylation analysis revealed similar high methylation of the region upstream of the CTCF binding sites in both blue-eggshelled and white-eggshelled ducks. However, DNA methylation levels downstream of the binding sites were decreased and 35% lower in blue-eggshelled ducks than in white-eggshelled ducks. Consistent with the in vitro regulatory pattern of causative sites, ABCG2 exhibited higher expression in uteruses of blue-eggshelled ducks and also showed polarized distribution in their endometrial epithelial cells, distributing at the apical surface of endometrial epithelial cells and with orientation toward the uterine cavity, where the eggshell is pigmented. In conclusion, our results suggest that two cis-regulatory SNPs upstream of ABCG2 are the causative mutations for blue eggshells in ducks. The blue eggshell variant up-regulated ABCG2 expression through recruiting CTCF binding, which may function as a barrier element to shield the downstream region from high methylation levels present upstream. ABCG2 was identified as the only candidate causative gene for blue eggshells; it may function as an efflux transporter of biliverdin to the uterine cavity. Public Library of Science 2020-11-13 /pmc/articles/PMC7688135/ /pubmed/33186356 http://dx.doi.org/10.1371/journal.pgen.1009119 Text en © 2020 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chen, Li
Gu, Xiaorong
Huang, Xuetao
Liu, Rui
Li, Jinxiu
Hu, Yiqing
Li, Guoqin
Zeng, Tao
Tian, Yong
Hu, Xiaoxiang
Lu, Lizhi
Li, Ning
Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck
title Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck
title_full Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck
title_fullStr Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck
title_full_unstemmed Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck
title_short Two cis-regulatory SNPs upstream of ABCG2 synergistically cause the blue eggshell phenotype in the duck
title_sort two cis-regulatory snps upstream of abcg2 synergistically cause the blue eggshell phenotype in the duck
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688135/
https://www.ncbi.nlm.nih.gov/pubmed/33186356
http://dx.doi.org/10.1371/journal.pgen.1009119
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