Imprinted X chromosome inactivation in marsupials

This research examines the contrasting mechanisms of eutherian and marsupial X chromosome inactivation (XCI) by investigating one of the key differences: paternal imprinting in marsupials. Analysis of DNA methylation patterns on the marsupial X chromosome during spermatogenesis revealed that genes o...

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Detalles Bibliográficos
Autores: Milton, Ashley M.|||0000-0002-2847-2777, Marin Gual, Laia|||0000-0003-1480-0976, Lister, Nicholas|||0000-0002-6597-4784, McIntyre, Kim L., Grady, Patrick G. S., Laird, Melanie K., Bond, Donna M., Hore, Timothy A.|||0000-0002-6735-225X, O'Neill, Rachel J., Pask, Andrew J.|||0000-0002-1900-2263, Renfree, Marilyn B.|||0000-0002-4589-0436, Ruiz Herrera Moreno, Aurora|||0000-0003-3868-6151, Waters, Paul D.|||0000-0002-4689-8747
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:317822
Acceso en línea:https://ddd.uab.cat/record/317822
https://dx.doi.org/urn:doi:10.1073/pnas.2412185121
Access Level:acceso abierto
Palabra clave:DNA methylation
Marsupial
Imprinting
X chromosome inactivation
Spermatogenesis
Descripción
Sumario:This research examines the contrasting mechanisms of eutherian and marsupial X chromosome inactivation (XCI) by investigating one of the key differences: paternal imprinting in marsupials. Analysis of DNA methylation patterns on the marsupial X chromosome during spermatogenesis revealed that genes on the paternal X chromosome exhibit a DNA methylation profile akin to the "silent" profile of genes on inactive X chromosomes in female somatic cells. This observation suggests a preexisting, silent DNA methylation landscape on the paternal X chromosome upon fertilization, which we hypothesize is the long sought-after imprint governing paternal XCI in marsupials. 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 sought-after imprint for paternal XCI in marsupials.