1022-7954/05/4107- © 2005 Pleiades Publishing, Inc.
Russian Journal of Genetics, Vol. 41, No. 7, 2005, pp. 720–727. Translated from Genetika, Vol. 41, No. 7, 2005, pp. 884–893.
Original Russian Text Copyright © 2005 by Shidlovskii, Nabirochkina.
In nuclei of eukaryotic cells, DNA is packaged in
intricately organized ﬁbers, chromatin, which makes it
inaccessible to many transcription factors. Transcrip-
tion activation has been shown to be associated with
reorganization of the chromatin structure, while gene
repression is accompanied by restoring the initial con-
densed chromatin state. Thus, transcriptional regulation
can occur at the chromatin level [1, 2].
The structural unit of chromatin is the nucleosome.
The main part of the nucleosome is formed by an
octamer consisting of four histones (H2A, H2B, H3,
and H4) and a 147-bp DNA region wrapped around the
octamer. The structure of the histone octamer is as fol-
lows: histones H3 and H4 form tetramer (H3)
ﬂanked by dimers H2A–H2B. The DNA makes 1.65
turns around the histone octamer; stretches of 20 to
50 bp of linker DNA separate nucleosomes. Thus is
formed a chain of repeated units, which is a ﬁber 10 nm
in diameter. The formation of ﬁbers is also mediated by
linker histone H1, interacting with both linker DNA
and the nucleosome histones. The formation of nucleo-
somes is the ﬁrst level of DNA compaction in the
nucleus. Further compaction is accomplished through
the interaction of nucleosomes with one another and
with a number of nonhistone proteins [3–5].
Histone proteins have a speciﬁc structure. Each his-
tone has a central domain (the histone core) and the N-
terminal unstructured region, which is referred to as the
“histone tail” and consists of 15 to 30 amino-acid resi-
dues. This region is involved in histone–histone and
histone–DNA interactions within the octamer. Histone
tails are positively charged and serve as target for vari-
ous posttranslational modiﬁcations, changing their
charge or conformation and affecting their interaction
with DNA or other proteins, which inﬂuences the tran-
scription level .
In addition to chemical modiﬁcation of histones,
their protein variants are known, the presence of which
also has an effect on transcription rate: variant H3.3 is
speciﬁcally transported to the actively transcribed loci,
variant H2AZ suppresses the chromatin spreading to
the regions of active transcription .
The nucleosome presence on DNA restricts the gene
expression, because nucleosomes usually inhibit bind-
ing of transcription factors. The general reduction of
the nucleosomes number in the nucleus results in the
general transcription activation . The cell harbors a
number of complexes that are involved in transcription
regulation by changing the chromatin structure. These
complexes are classiﬁed into two main groups:
—ATP-dependent complexes that locally alter the
physical chromatin structure (remodeling complexes);
—complexes that accomplish various chemical
modiﬁcations of histone tails.
Generally, the transcription initiation requires chro-
matin modiﬁcation and remodeling in the region of pro-
moter and regulatory sequences to provide access to the
DNA template for basal transcription factors and
diverse activators .
Some transcription factors can bind to the intact chro-
matin DNA template; interactions of a single molecule
of the factor with the nucleosome are weak but become
stronger in the presence of several binding sites, owing to
cooperative binding. Moreover, transcription factors can
bind to the linker DNA region. The ability of the factors
to bind to the chromatin may depend on the nucleotide
DNA sequence and the nucleosome position. It is
thought that particular transcription factors, after having
bound to the condensed chromatin, recruit remodeling
and modifying complexes . Both activators (e.g., glu-
cocorticoid receptor) and basal transcription factors
(TBP and TFIIB) can bind to chromatin .
Nucleosomes prevent transcriptional elongation.
Apparently, in this process the nucleosomes located
The Effect of Chromatin Remodeling and Modification
on RNA-Polymerase-Mediated Transcription Initiation
Yu. V. Shidlovskii
and E. N. Nabirochkina
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia; fax: (095) 135-41-05; e-mail: firstname.lastname@example.org
Center for Medical Research of Oslo University, Moscow, 119334 Russia
Received December 28, 2004
—As eukaryotes are characterized by the presence of chromatin (intricately packaged DNA), special
mechanisms are required for preparing the DNA template for operation of the transcription machinery.
Recently, a close association between the chromatin state and transcription was found and numerous transcrip-
tion factors modifying the physical and chemical chromatin state were revealed. This review presents a brief
description of transcription initiation on the DNA template within chromatin.