The making of a Barr body: the mosaic of factors that eXIST on the mammalian inactive X chromosome

Abstract

During X-chromosome inactivation (XCI), nearly an entire X chromosome is permanently silenced and converted into a Barr body, providing dosage compensation for eutherians between the sexes. XCI is facilitated by the upregulation of the long non-coding RNA gene, XIST, which coats its chromosome of origin, recruits heterochromatin factors, and silences gene expression. During XCI, at least two distinct types of heterochromatin are established, and in this review we discuss the enrichment of facultative heterochromatin marks such as H3K27me3, H2AK119ub, and macroH2A as well as pericentric heterochromatin marks such as HP1, H3K9me3, and H4K20me3. The extremely stable maintenance of silencing is a product of reinforcing interactions within and between these domains. This paper "Xplores" the current knowledge of the pathways involved in XCI, how the pathways interact, and the gaps in our understanding that need to be filled.

Sex Drives Dimorphic Immune Responses to Viral Infections

“…Barr bodies are formed as a result of Xist gene expression and histone modification making one of the X chromosomes inactive in every cell (98). This process, which is exclusive to XX somatic cells, is random, leading to cells with active maternal or paternal X, and compensates X gene dosages in all somatic cells (14). The gene products of X or Y gene also facilitate epigenetic modifications on the DNA of an individual.…”

Derivation of consensus inactivation status for X-linked genes from genome-wide studies

“…XCI is thought to be initiated by the lncRNA XIST, which is expressed specifically from the Xi. Early in development, XIST spreads along one of the X chromosomes and allows for the recruitment of histone-modifying enzymes to make cooperative silencing modifications such as H3K27me3, ubH2A, H4K20me3, and H3K9me3 (reviewed in [ 17 ]). DNA methylation (DNAm) is another epigenetic mark associated with X inactivation, and blocking DNAm with 5-azacytidine allows reactivation of X-linked genes in human-mouse hybrid cells [ 18 ].…”

Dosage Compensation in Drosophila—a Model for the Coordinate Regulation of Transcription

“…The discovery of dosage compensation in Drosophila predated the study of the analogous phenomenon in mammals, where the facultative heterochromatization of one of the two X chromosomes in females involves the spread of noncoding RNAs (ncRNAs), as a harbinger of covalent modifications to both DNA and histones (reviewed in Dixon-McDougall and Brown 2016). Similarly it led to the discovery of dosage compensation in Caenorhabditis elegans, where the limited downregulation of both X chromosomes in hermaphrodites involves a subset of proteins and factors that are normally engaged in chromosome condensation during cell division (reviewed in Meyer 2010).…”