Imprinted X chromosome inactivation in marsupials: The paternal X arrives at the egg with a silent DNA methylation profile

• 成果类型: Article
• 署名作者: Milton, Ashley M.; Marin-Gual, Laia; Lister, Nicholas C.; McIntyre, Kim L.; Grady, Patrick G. S.; Laird, Melanie K.; Bond, Donna M.; Hore, Timothy A.; O'Neill, Rachel J.; Pask, Andrew J.; Renfree, Marilyn B.; Ruiz-Herrera, Aurora; Waters, Paul D.
• 署名单位: University of New South Wales Sydney; Autonomous University of Barcelona; Autonomous University of Barcelona; University of Connecticut; University of Connecticut; University of Otago; University of Melbourne
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10441
• DOI: 10.1073/pnas.2412185121
• 发表日期: 2024-09-03
• 关键词: germ-cell development; gene; mouse; EVOLUTION; rna; islands; mammals; region

摘要

X chromosome inactivation (XCI) is an epigenetic process that results in the transcriptional silencing of one X chromosome in the somatic cells of females. This phenomenon is common to both eutherian and marsupial mammals, but there are fundamental differences. In eutherians, the X chosen for silencing is random. DNA methylation on the eutherian inactive X is high at transcription start sites (TSSs) and their flanking regions, resulting in universally high DNA methylation. This contrasts XCI in marsupials where the paternally derived X is always silenced, and in which DNA methylation is low at TSSs and flanking regions. Here, we examined the DNA methylation status of the tammar wallaby X chromosome during spermatogenesis to determine the DNA methylation profile of the paternal X prior to and at fertilization. Whole genome enzymatic methylation sequencing was carried out on enriched flow- sorted populations of premeiotic, meiotic, and postmeiotic cells. We observed that the X displayed a pattern of DNA methylation from spermatogonia to mature sperm that reflected the inactive X in female somatic tissue. Therefore, the paternal X chromosome arrives at the egg with a DNA methylation profile that reflects the transcriptionally silent X in adult female somatic tissue. We present this epigenetic signature as a candidate for the long soughtafter imprint for paternal XCI in marsupials.