Specific patterns of histone marks accompany X chromosome inactivation in a marsupial

Abstract

The inactivation of one of the two X chromosomes in female placental mammals represents a remarkable example of epigenetic silencing. X inactivation occurs also in marsupial mammals, but is phenotypically different, being incomplete, tissuespecific and paternal. Paternal X inactivation occurs also in the extraembryonic cells of rodents, suggesting that imprinted X inactivation represents a simpler ancestral mechanism. This evolved into a complex and random process in placental mammals under the control of the XIST gene, involving notably variant and modified histones. Molecular mechanisms of X inactivation in marsupials are poorly known, but occur in the absence of an XIST homologue. We analysed the specific pattern of histone modifications using immunofluorescence on metaphasic chromosomes of a model kangaroo, the tammar wallaby. We found that all active marks are excluded from the inactive X in marsupials, as in placental mammals, so this represents a common feature of X inactivation throughout mammals. However, we were unable to demonstrate the accumulation of inactive histone marks, suggesting some fundamental differences in the molecular mechanism of X inactivation between marsupial and placental mammals. A better understanding of the epigenetic mechanisms underlying X inactivation in marsupials will provide important insights into the evolution of this complex process.

The origin and evolution of vertebrate sex chromosomes and dosage compensation

“…However, interesting observations have come from several recent studies of representative Australian and American marsupials, using immunofluorescence to examine histone marks that are associated with XCI in human and mouse. The inactive marsupial X lost epigenetic modifications associated with transcription during interphase (Chaumeil et al, 2011) and metaphase (Koina et al, 2009;Rens et al, 2010), and the nuclear territory that harbours Xi was devoid of RNA Pol II (Chaumeil et al, 2011). These observations established that the marsupial Xi is situated in a transcriptionally inert nuclear compartment, as it is in eutherian mammals.…”

“…Differential acetylation had been observed on the X chromosomes in female tammar wallaby (Wakefield et al, 1997), as was enrichment of an active histone methylation mark (presumably on the active X) (Wakefield et al, 1997;Koina et al, 2009), and no differential DNA methylation differences were detected (Piper et al, 1993;Loebel and Johnston, 1996). However, interesting observations have come from several recent studies of representative Australian and American marsupials, using immunofluorescence to examine histone marks that are associated with XCI in human and mouse.…”

“…Some modifications were completely absent from the marsupial Xi (Koina et al, 2009;Chaumeil et al, 2011), whereas others were restricted to specific windows of the cell cycle (Chaumeil et al, 2011). Of considerable surprise was the accumulation of marks on Xi that are associated with pericentromeric heterochromatin (Mahadevaiah et al, 2009;Rens et al, 2010;Chaumeil et al, 2011;Zakharova et al, 2011).…”

Mechanistic concepts in X inactivation underlying dosage compensation in mammals

“…The marsupial imprinted X chromosome shares some features with the Xi of placental mammals. It lacks histone modifications associated with active chromatin consistent with its repressed state (Koina et al, 2009). A recent study shows that marsupial imprinted X inactivation also involves reactivation of the X chromosome after male meiosis and histone H3 lysine 27 methylation (Mahadevaiah et al, 2009).…”

“…The Xic region has undergone repeated genetic rearrangements during the evolution of mammals. In marsupials dosage compensation is achieved by inactivation of the paternally inherited X chromosome (Graves, 1996;Koina et al, 2009). As marsupial Xist has not been identified it is likely that an alternative mechanism of imprinted X inactivation exists.…”