Clinical Epigenetic Therapies Disrupt Sex Chromosome Dosage Compensation in Human Female Cells.

ABSTRACT: Sex chromosome gene dosage compensation is required to ensure equivalent levels of X-linked gene expression between males (46, XY) and females (46, XX). To achieve similar expression, X-chromosome inactivation (XCI) is initiated in female cells during early stages of embryogenesis. Within each cell, either the maternal or paternal X chromosome is selected for whole chromosome transcriptional silencing, which is initiated and maintained by epigenetic and chromatin conformation mechanisms. With the emergence of small-molecule epigenetic inhibitors for the treatment of disease, such as cancer, the epigenetic mechanism underlying XCI may be inadvertently targeted. Here, we test 2 small-molecule epigenetic inhibitors being used clinically, GSK126 (a histone H3 lysine 27 methyltransferase inhibi

SUBMITTER: Laskowski AI 

PROVIDER: S-EPMC6424500 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature