Oral Presentation 45th Lorne Genome Conference 2024

Circadian rhythm tempers establishment of X chromosome inactivation (#18)

Andrew Keniry 1 , Kelsey Breslin 1 , Matthew Ritchie 1 , Marnie Blewitt 1
  1. Walter and Eliza Hall Institute, Parkville, VIC, Australia

X chromosome inactivation (XCI) is the mammalian compensation mechanism that ensures equal gene dosage between XX females and XY males, resulting in near complete silencing of one female X chromosome. The silencing process is necessarily complex, multilayered and not fully understood despite significant research effort. Using unbiased screens, we discovered that the establishment of XCI is controlled by circadian rhythm. Female mouse embryonic stem cells lack both XCI and circadian rhythm and these epigenetic processes must be co-established upon differentiation, with circadian rhythm tempering the rate at which XCI proceeds. We also find that the day night cycle of the mother regulates establishment of XCI in blastocyst outgrowths two weeks ex-vivo, suggesting an epigenetic memory of the mother’s circadian rhythm that contributes to gene silencing in the embryo.