RESUMO
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.
Assuntos
Metilação de DNA , Inativação do Cromossomo X , Cromossomo X , Animais , Inativação do Cromossomo X/genética , Masculino , Feminino , Cromossomo X/genética , Impressão Genômica , Espermatogênese/genética , Macropodidae/genética , Óvulo/metabolismo , Marsupiais/genética , Espermatozoides/metabolismo , Epigênese GenéticaRESUMO
Heteromorphic sex chromosomes (XY or ZW) present problems of gene dosage imbalance between sexes and with autosomes. A need for dosage compensation has long been thought to be critical in vertebrates. However, this was questioned by findings of unequal mRNA abundance measurements in monotreme mammals and birds. Here, we demonstrate unbalanced mRNA levels of X genes in platypus males and females and a correlation with differential loading of histone modifications. We also observed unbalanced transcripts of Z genes in chicken. Surprisingly, however, we found that protein abundance ratios were 1:1 between the sexes in both species, indicating a post-transcriptional layer of dosage compensation. We conclude that sex chromosome output is maintained in chicken and platypus (and perhaps many other non therian vertebrates) via a combination of transcriptional and post-transcriptional control, consistent with a critical importance of sex chromosome dosage compensation.
Assuntos
Galinhas , Mecanismo Genético de Compensação de Dose , Ornitorrinco , Cromossomos Sexuais , Animais , Galinhas/genética , Cromossomos Sexuais/genética , Masculino , Feminino , Ornitorrinco/genética , Transcrição Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
The marsupial specific RSX lncRNA is the functional analogue of the eutherian specific XIST, which coordinates X chromosome inactivation. We characterized the RSX interactome in a marsupial representative (the opossum Monodelphis domestica), identifying 135 proteins, of which 54 had orthologues in the XIST interactome. Both interactomes were enriched for biological pathways related to RNA processing, regulation of translation, and epigenetic transcriptional silencing. This represents a remarkable example showcasing the functional coherence of independently evolved lncRNAs in distantly related mammalian lineages.
Assuntos
RNA Longo não Codificante , Inativação do Cromossomo X , Animais , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/genética , Monodelphis/genética , Monodelphis/metabolismoRESUMO
DNA methylation is a key epigenetic modification in vertebrate genomes known to be involved in the regulation of gene expression, X chromosome inactivation, genomic imprinting, chromatin structure, and control of transposable elements. DNA methylation is common to all eukaryote genomes, but we still lack a complete understanding of the variation in DNA methylation patterns on sex chromosomes and between the sexes in diverse species. To better understand sex chromosome DNA methylation patterns between different amniote vertebrates, we review literature that has analyzed the genome-wide distribution of DNA methylation in mammals and birds. In each system, we focus on DNA methylation patterns on the autosomes versus the sex chromosomes.