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The regulation of methylation on the Z chromosome and the identification of multiple novel Male Hyper-Methylated regions in the chicken
Science for Life Laboratory, Department of Environmental Science, Stockholm University, Stockholm, Sweden.
AVIAN Behavioural Genomics and Physiology Group, Linköping University, Linköping, Sweden.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0000-0003-1902-3002
Physiology and Environmental Toxicology Program, Department of Organismal Biology, Uppsala University, Uppsala, Sweden.
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2024 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 20, no 3, article id e1010719Article in journal (Refereed) Published
Abstract [en]

DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. To investigate how variation in DNA methylation is regulated on the Z chromosome we utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals. The relatively large numbers of individuals allowed us to identify additional genomic MHM regions on the Z chromosome that were significantly differentially methylated between the sexes. These regions appear to down-regulate local gene expression in males, but not remove it entirely (unlike the lncRNAs identified in the initial MHM regions). These MHM regions were further tested and the most balanced genes appear to show decreased expression in males, whilst methylation appeared to be far more correlated with gene expression in the less balanced, as compared to the most balanced genes. In addition, trans effect hotspots were also identified that were based on the autosomes but affected the Z, and also that were based on the Z chromosome but that affected autosomal DNA methylation regulation. In addition, quantitative trait loci (QTL) that regulate variation in methylation on the Z chromosome, and those loci that regulate methylation on the autosomes that derive from the Z chromosome were mapped. Trans-effect hotspots were also identified that were based on the autosomes but affected the Z, and also one that was based on the Z chromosome but that affected both autosomal and sex chromosome DNA methylation regulation. We show that both cis and trans loci that originate from the Z chromosome never exhibit an interaction with sex, whereas trans loci originating from the autosomes but affecting the Z chromosome always display such an interaction. Our resultshighlight how additional MHM regions are actually present on the Z chromosome, and theyappear to have smaller-scale effects on gene expression in males. Quantitative variation in methylation is also regulated both from the autosomes to the Z chromosome, and from the Zchromosome to the autosomes.

Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2024. Vol. 20, no 3, article id e1010719
National Category
Genetics and Genomics
Identifiers
URN: urn:nbn:se:umu:diva-222687DOI: 10.1371/journal.pgen.1010719ISI: 001181686300001PubMedID: 38457441Scopus ID: 2-s2.0-85187319752OAI: oai:DiVA.org:umu-222687DiVA, id: diva2:1847071
Funder
Swedish Research Council, 2018-04421Carl Tryggers foundation Available from: 2024-03-26 Created: 2024-03-26 Last updated: 2025-02-07Bibliographically approved

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Churcher, Allison M

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