X chromosome inactivation (X-inactivation) in female mammals is triggered by differential upregulation of the Xist gene on one of the two X chromosomes and subsequent coating of the X in cis with its non-coding transcripts. Although targeted mutation has clearly shown that Xist is essential for X-inactivation in cis, the molecular mechanism by which Xist RNA induces chromosome silencing is larg...

Most models of tumorigenesis assume that tumors are monoclonal in origin. This conclusion is based largely on studies using X chromosome-linked markers in females. One important factor, often ignored in such studies, is the distribution of X-inactivated cells in tissues. Because lyonization occurs early in development, many of the progeny of a single embryonic stem cell are grouped together in ...

Serological diagnosis is a critical component for disease surveillance and is important to address the increase in incidence and disease burden of alphaviruses, such as the chikungunya (CHIKV) and Ross River (RRV) viruses. The gold standard for serological diagnosis is the plaque reduction neutralization test (PRNT), which demonstrates the neutralizing capacity of serum samples after the remova...

Mammals compensate for unequal X-linked gene dosages between the sexes by inactivating one X chromosome in the female. In marsupials and in the early mouse embryo, X chromosome inactivation (XCI) is imprinted to occur selectively on the paternal X chromosome (X(P)). The mechanisms and events underlying X(P) imprinting remain unclear. Here, we find that the imprinted X(P) can be functionally div...

Germ cells have the same DNA sequence as somatic cells, but the processes that act on their chromatin are different. Germline chromatin undergoes a series of dramatic remodeling events during the life cycle of an organism. Different aspects of germline chromatin have been dissected in recent years, such as differences between the sex chromosomes and autosomes in histone variants and modificatio...

Dosage compensation in mammals occurs by X inactivation, a silencing mechanism regulated in cis by the X inactivation center (Xic). In response to developmental cues, the Xic orchestrates events of X inactivation, including chromosome counting and choice, initiation, spread, and establishment of silencing. It remains unclear what elements make up the Xic. We previously showed that the Xic is co...

The pseudoautosomal region (PAR) is a unique and specialized segment on the mammalian sex chromosomes with known functions in male meiosis and fertility. Detailed molecular studies of the region in human and mouse show dramatic differences between the 2 PARs. Recent mapping efforts in horse, dog/cat, cattle/ruminants, pig and alpaca indicate that the PAR also varies in size and gene content bet...

A good deal of sex differences in kidney disease is attributable to sex differences in the function of genes on the X chromosome. Males are uniquely vulnerable to mutations in their single copy of X-linked genes, whereas females are often mosaic, having a mixture of cells expressing different sets of X-linked genes. This cellular mosaicism created by X inactivation in females is most often adva...

In female mammals, a single X chromosome is stably and heritably silenced early in embryogenesis. The inactive X is characterized by asynchronous DNA replication and epigenetic chromatin modifications, including DNA methylation, histone H3/H4 hypoacetylation, and incorporation of a variant histone macroH2A. X inactivation is initiated by a cis-acting RNA molecule, the X-inactive specific transc...

These studies address whether XIST RNA is properly localized to the X chromosome in somatic cells where human XIST expression is reactivated, but fails to result in X inactivation (Tinker, A.V., and C.J. Brown. 1998. Nucl. Acids Res. 26:2935-2940). Despite a nuclear RNA accumulation of normal abundance and stability, XIST RNA does not localize in reactivants or in naturally inactive human X chr...