ISSN 10227954, Russian Journal of Genetics, 2010, Vol. 46, No. 10, pp. 1233–1235. © Pleiades Publishing, Inc., 2010.
Original Russian Text © K.E. Orischenko, E.A. Elisaphenko, S.M. Zakian, 2010, published in Genetika, 2010, Vol. 46, No. 10, pp. 1397–1400.
Females of higher mammal are characterized by
gene dose compensation occurring during the early
development due to inactivation of one of the X chro
mosomes. The key role in the Xchromosome inacti
vation belongs to the
XInactivate Specific Tran
gene encoding large (more than 17 kb) nontrans
lating nuclear RNA.
RNA is accumulated and
transcribed from the X chromosome, resulting in its
heterochromatinization and transcription inactivation
of almost all Xchromosome genes .
Cells differentiating into embryo tissues are char
acterized by the random inactivation either of the
paternal (Xp) or maternal (Xm) X chromosome. This
process is stochastic and independent for each cell.
Once set in, the nonactive state is maintained in con
secutive cell divisions, which causes mosaicism in all
tissues in females, i.e., they consist of two types of cells
with active Xp or Xm approximately in the equal ratio.
However, cases with predominant (nonrandom,
skewed) inactivation of one of the two X chromosomes
are known. One of the reasons of such inactivation
includes stochastic factors. The process of Xchromo
some inactivation is stochastic, as such; moreover, the
number of inner cell mass (
) is small at the blas
tocyst stage, which could result in an unnonequal dis
tribution of cells with active Xp or Xm during the for
mation of various embryo tissues, which in turn could
cause wrong detection of nonrandom inactivation.
Mutations in the genes of one of the two X chromo
somes are assumed to be another reason. These muta
tions could result in both increased and decreased
growth parameters in cells bearing mutation on the
active X chromosome compared to cells with the active
intact X chromosome. Accordingly, as a result of cell
selection, one cell population would prevail over the
other. Human blood cells are a typical example of such
inactivation pattern detection . Another explana
tion of nonrandom inactivation involves mutations of
genetic elements directly involved in the inactivation
process at the stage of selection of the future inactive
X chromosome. Such mutations are known to exist in
mouse and human ; mice also have the
known for its influence on the selection of the future in
active X chromosome .
The main evidence concerning inactivation mech
anism was obtained for the classic models of genetic
research, human and mouse. The present study was
vole species due to the unique
property of this model: nonrandom Xchromosome
inactivation in intraspecific hybrid females. Namely,
were characterized by the active state of the X chromo
some inherited from
in 80% of cells . The
mechanism of nonrandom inactivation remains
unclear. However, one reason may be differences in the
expression level of
gene alleles. Such models are
highly important, since the data revealed using non
standard models may contribute to the understanding
of Xchromosome inactivation mechanisms.
The minimal promoter of
ized by G to A singlenucleotide substitution at posi
tion –43 bp relatively to the site of transcription initi
ation. The C(43)G mutation in the
moter in mouse and human results in predominant
inactivation of the X chromosome carrying the muta
tion, while the C(43)A mutation, conversely, causes a
higher frequency of cases with the native Xchromo
some inactivation. This could be explained by a signif
icant increase in the effectiveness of CTCF transcrip
Role of G(43)A Polymorphism in the Promoter Region
Gene in Nonrandom XChromosome
Inactivation in Intraspecific Hybrid Voles
K. E. Orischenko, E. A. Elisaphenko, and S. M. Zakian
Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia;
Received January 28, 2010.
—Interaction of transcription factor CTCF with the minimal promoter of
gene was investigated
in intraspecific hybrids of common voles. CTCF was shown to bind with the minimal promoter region
However, the EMSA experiments resulted in the absence of interaction between the CTCF factor and its
potential binding site. Probably, G(43)A substitution influences binding efficacy of another transcription
factor such as activator protein 2, AP2.