| Autor: |
Gabriel Manske, Kelsey Jorgensen, Binbin Ma, Mansour Aboelenain, Catherine Tower, Saikat Chakraborty, Rajesh Ranjan, Arunika Das, Michael A. Lampson, Ben E. Black, Karen Schindler, Xin Chen, Saher Sue Hammoud |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.10.27.514094 |
| Popis: |
SummaryThe CENP-A histone variant epigenetically defines centromeres, where its levels and locations are precisely maintained through mitotic cell divisions. However, differences in centromere CENP-A propagation in soma versus female/male germline remains poorly understood. Here, we generated CenpamScarletmice and followed CENP-A dynamics in gametes, zygotes, and embryos. We found that, unlike somatic cells, progenitor female and male germ cells carry high centromeric CENP-A levels that decrease upon terminal differentiation. The reduction in CENP-A is differentially regulated between sexes, resulting in a ten-fold higher level in oocytes compared to sperm. In the zygote, the parent-of-origin CENP-A asymmetry is equalized prior to initial S-phase by redistribution of nuclear CENP-A from maternal to paternal chromosomes. Redistribution of CENP-A requires both CDK1/2 and PLK1 centromeric machinery. These experiments provide direct evidence for resetting of epigenetically imprinted centromeres in early pronuclear stage embryos and imply a mechanism to sense the non-equivalency of parental chromosomes.HighlightsIncreased CENP-A density at centromeres is a conserved property of germline stem cells while CENP-A reduction is coincident with germ cell differentiationPaternal and maternal CENP-A containing nucleosomes are intergenerationally inheritedCENP-A density at centromeres differs between male and female mature gametesUpon fertilization, maternal nuclear CENP-A is redistributed to equalize with parental CENP-ACENP-C and MIS18BP1 are asymmetrically enriched in the parental pronuclei in accordance with CENP-A asymmetry.Licensing for centromere equalization begins before zygotic DNA replication |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
