In:
Genome Medicine, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2023-03-28)
Kurzfassung:
Sex chromosome aneuploidies (SCAs) give rise to a broad range of phenotypic traits and diseases. Previous studies based on peripheral blood samples have suggested the presence of ripple effects, caused by altered X chromosome number, affecting the methylome and transcriptome. Whether these alterations can be connected to disease-specific tissues, and thereby having clinical implication for the phenotype, remains to be elucidated. Methods We performed a comprehensive analysis of X chromosome number on the transcriptome and methylome in blood, fat, and muscle tissue from individuals with 45,X, 46,XX, 46,XY, and 47,XXY. Results X chromosome number affected the transcriptome and methylome globally across all chromosomes in a tissue-specific manner. Furthermore, 45,X and 47,XXY demonstrated a divergent pattern of gene expression and methylation, with overall gene downregulation and hypomethylation in 45,X and gene upregulation and hypermethylation in 47,XXY. In fat and muscle, a pronounced effect of sex was observed. We identified X chromosomal genes with an expression pattern different from what would be expected based on the number of X and Y chromosomes. Our data also indicate a regulatory function of Y chromosomal genes on X chromosomal genes. Fourteen X chromosomal genes were downregulated in 45,X and upregulated in 47,XXY, respectively, in all three tissues ( AKAP17A , CD99 , DHRSX , EIF2S3 , GTPBP6 , JPX , KDM6A , PP2R3B , PUDP , SLC25A6 , TSIX , XIST , ZBED1 , ZFX ). These genes may be central in the epigenetic and genomic regulation of sex chromosome aneuploidies. Conclusion We highlight a tissue-specific and complex effect of X chromosome number on the transcriptome and methylome, elucidating both shared and non-shared gene-regulatory mechanism between SCAs.
Materialart:
Online-Ressource
ISSN:
1756-994X
DOI:
10.1186/s13073-023-01169-4
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2023
ZDB Id:
2484394-5
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