Biology subjects

Balaton, B. P.

Publications and source records attributed to Balaton, B. P..

2 recordsLinked to original sources

bioRxiv2021

Contribution of epigenetic changes to escape from X-chromosome inactivation

BackgroundX-chromosome inactivation (XCI) is the epigenetic inactivation of one of two X chromosomes in XX eutherian mammals. The facultatively heterochromatic inactive X chromosome acquires many chromatin changes including DNA methylation and histone modifications. Despite these changes, some genes escape or variably escape from inactivation, and to the extent that they have been studied, epigenetic marks correlate with expression. ResultsWe downloaded data from the International Human Epigenome Consortium and compared previous XCI status calls to DNA methylation, H3K4me1, H3K4me3, H3K9me3, H3K27ac, H3K27me3 and H3K36me3. At genes subject to XCI we found heterochromatic marks enriched, and euchromatic marks depleted on the inactive X when compared to the active X. Similar results were seen for genes escaping XCI although with diminished effect with H3K27me3 being most enriched. Using sample-specific XCI status calls made using allelic expression or DNA methylation we also compared differences between samples with opposite XCI statuses at variably escaping genes. We found some marks significantly differed with XCI status, but which marks were significant was not consistent between genes. We trained a model to predict XCI status from these epigenetic marks and obtained over 75% accuracy for genes escaping and over 90% for genes subject to XCI. This model allowed us to make novel XCI status calls for genes without allelic differences or CpG islands required for other XCI status calling methods. Using these calls to examine a domain of variably escaping genes, we saw XCI status vary at the level of individual genes and not at the domain level. ConclusionHere we show that epigenetic marks differ between genes that are escaping and those subject to XCI, and that genes escaping XCI still differ between the active and inactive Xs. We show epigenetic differences at variably escaping genes, between samples escaping and those subject to XCI. Lastly we show gene-level regulation of variably escaping genes within a domain.

genetics↗

bioRxiv2020

Cross-species examination of X-chromosome inactivation highlights domains of escape from silencing

BackgroundX-chromosome inactivation (XCI) in eutherian mammals is the epigenetic inactivation of one of the two X chromosomes in XX females in order to compensate for dosage differences with XY males. Not all genes are inactivated, and the proportion escaping from inactivation varies between human and mouse (the two species that have been extensively studied). ResultsWe used DNA methylation to predict the XCI status of X-linked genes with CpG islands across 12 different species: human, chimp, bonobo, gorilla, orangutan, mouse, cow, sheep, goat, pig, horse and dog. We determined the XCI status of 342 CpG islands on average per species, with most species having 80-90% of genes subject to XCI. Mouse was an outlier, with a higher proportion of genes subject to XCI than found in other species. Sixteen genes were found to have discordant X-chromosome inactivation statuses across multiple species, with five of these showing primate-specific escape from XCI. These discordant genes tended to cluster together within the X chromosome, along with genes with similar patterns of escape from XCI. CTCF- binding, ATAC-seq signal and LTR repeats were enriched at genes escaping XCI when compared to genes subject to XCI; however, enrichment was only observed in three or four of the species tested. LINE and DNA repeats showed enrichment around subject genes, but again not in a consistent subset of species. ConclusionsIn this study we determined XCI status across 12 species, showing mouse to be an outlier with few genes that escape inactivation. Inactivation status is largely conserved across species. The clustering of genes that change XCI status across species implicates a domain-level control. In contrast, the relatively consistent, but not universal correlation of inactivation status with enrichment of repetitive elements or CTCF binding at promoters demonstrates gene-based influences on inactivation state. This study broadens enrichment analysis of regulatory elements to species beyond human and mouse.

genetics↗