1022-7954/04/4012- © 2004
Russian Journal of Genetics, Vol. 40, No. 12, 2004, pp. 1430–1433. Translated from Genetika, Vol. 40, No. 12, 2004, pp. 1722–1425.
Original Russian Text Copyright © 2004 by Kullyev, Savytskaya, Georgiev, Gruzdeva.
) homeotic gene is respon-
sible for the formation of the abdominal segments in
Its regulatory region of
approximately 50 kb consists of chromatin domains,
each controlling expression in a single segment [1, 2]
(Fig. 1). The domains each contain at least one
enhancer, which activates expression of the
in early embryo development, and a silencer, which
maintains the expression pattern during development.
Molecular genetic analysis showed that the
locus contains boundary elements MCP, Fab-7, and
Fab-8, which ensure the functional independence of the
regulatory domains of the
gene and act as insu-
lators [3, 4]. So-called Polycomb responsive elements
(PREs) are located in the immediate vicinity of the
insulator or within the insulator and play a role in gene
silencing, which is essential for normal development.
Enhancers that must be nonfunctional in a particular
parasegment are inhibited by suppressor complexes
assembled from Polycomb group proteins on PREs.
Thus, MCP, Fab-7, and Fab-8 determine the boundary
between active and inactive chromatin regions. In each
chromatin domain, the enhancer is ﬂanked by two insu-
lators and is still capable of activating the promoter.
There is evidence that two Su(Hw) insulators inter-
act with each other and that their interaction either
strengthens or neutralizes insulation [5, 6]. These ﬁnd-
ings made it possible to advance a model that insulators
located in the regulatory region of the
selectively interact with each other to ensure efﬁcient
communication between the active enhancer and the
promoter and, on the other hand, complete inac-
tivation of the other enhancers . Yet recent studies
have shown that the Fab-7 and Fab-8 insulators do not
interact with each other or with the Su(Hw) insulator
. However, regulatory elements containing the Fab-7
or Fab-8 insulator and the adjacent silencer do interact
even when located on different chromosomes [4, 9, 10].
On the strength of these data, elements of the silencer
can be assumed to ensure the long-distance interaction
of insulators (Fig. 2b).
To check this assumption, we obtained a genetic
construct combining the Zw5 and Su(Hw) insulators
and silencers, which were placed in the regulatory
regions of the
genes (Fig. 2a).
The efﬁciency of the interaction between the silencers
was inferred from their ability to cooperatively sup-
press transcription of the
gene, which was
located between the silencers, and to neutralize the
effect of the Su(Hw) insulator. Experiments showed
that the silencers were ineffective in suppressing tran-
scription of the
gene or neutralizing the effect of
Roles of Silencers from the Regulatory Region
Gene and the Zw5 and Su(Hw) Insulators
in Regulating Gene Expression in
A. P. Kullyev, E. E. Savytskaya, P. G. Georgiev, and N. M. Gruzdeva
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 117334 Russia;
fax: (095)135-41-05; e-mail: email@example.com
Received May 24, 2004
—A study was made of the functional role of silencers in the long-distance interaction between insu-
lators. Transgenic lines containing the Su(Hw) and Zw5 insulators were analyzed. The silencers failed to efﬁ-
ciently suppress transcription of the
gene, nor did they neutralize the effect of the Su(Hw) insulator. The
long-distance interaction between insulators was assumed to depend on the combined effects of silencers, insu-
lators, and, possibly, some unidentiﬁed regulatory elements.
MCP Fab-6? Fab-7
Regulatory region of the
locus contains approximately 50 kb of 3'-
-regulatory DNA. The tran-
scription start site of the
gene is indicated with an arrow. The
iab-5, iab-6, iab-7
enhancers activate expression of
gene in parasegments 10–13, respectively. Presumably, the region contains two additional insulators, Fab-6 and Fab-9,
along with an insulator (UPR) located in the promoter region of the