The Questions of Developmental Biology

somatic cells, not germ cells. In female germ cells, the inactive X chromosome is reactivated
shortly before the cells enter meiosis (Gartler et al. 1973; Migeon and Jelalian 1977). Thus, in
early oocytes, both X chromosomes are unmethylated (and active). In each generation, X
chromosome inactivation has to be established anew.
Second, there are some exceptions to the rule of randomness in the inactivation pattern.
For instance, the first X chromosome inactivation in the mouse is seen in the fetal portion of the
placenta, where the paternally derived X chromosome is specifically inactivated (Tagaki 1974).
Third, X chromosome inactivation does not extend to every gene on the human X chromosome.
There are a few genes (such as that encoding steroid sulfatase) on both arms of the X
chromosome that "escape" X inactivation (Brown et al. 1997).
The fourth exception really ends up proving the rule. There are a few male mammals with
coat color patterns we would not expect to find unless the animals exhibited X chromosome
inactivation. Male calico and tortoiseshell cats are among these examples. These orange and
black spotted coat patterns are normally seen in females and are thought to result from random X
chromosome inactivation.* But rare males exhibit these coat patterns as well. How can this be? It
turns out that these cats are XXY. The Y chromosome makes them male, but one X chromosome
undergoes inactivation, just as in females, so there is only one active X per cell (Centerwall and
Benirschke 1973). Thus, these cats have cells with a Barr body and random X chromosome
inactivation. It is clear, then, that one mechanism for transcription-level control of gene regulation
is to make a large number of genes heterochromatic and thus transcriptionally inert.
*Although the terms calico and tortoiseshell are sometimes used synonymously, calico cats usually have white patches
as well (where no pigment is found). If the cat has an allele for orange pigment on one X chromosome and an allele for
black pigment on the other X chromosome, X inactivation will give patches of orange and black fur
The Mechanisms of X Chromosome Inactivation
The mechanisms of X chromosome inactivation are still poorly understood, but new
research is giving us some indication of the factors that may be involved in initiating and
maintaining a heterochromatic X chromosome.
Initiation of X Chromosome Inactivation: The Xist Gene
In 1991, Brown and her colleagues found an RNA transcript that was
made solely from the inactive X chromosome of humans. This transcript,
XIST, does not encode a protein. Rather, It stays within the nucleus and
interacts with the inactive X chromatin, forming an XIST-Barr body
complex (Brown et al. 1992). A similar situation exists in the mouse, in
which the transcript of the Xist gene is seen to coat the inactive X
chromosome (Figure 5.24; Borsani et al. 1991; Brockdorrf et al. 1992).
The Xist gene is an excellent candidate for the initiator of X inactivation. First, the
transcripts from the Xist gene are seen in mouse embryos prior to X chromosome inactivation,
which would be expected if this gene plays a role in initiating inactivation (Kay et al. 1993).