ISSN 10227954, Russian Journal of Genetics, 2016, Vol. 52, No. 1, pp. 29–37. © Pleiades Publishing, Inc., 2016.
Original Russian Text © M.M. Erokhin, A.I. Davydova, D.V. Lomaev, P.G. Georgiev, D.A. Chetverina, 2016, published in Genetika, 2016, Vol. 52, No. 1, pp. 37–46.
Gene transcription by RNA polymerase II is a key
step in realizing the genetic information. The genomes
of higher eukaryotes contain regulatory DNA
sequences that control gene transcription. Promoters
are the genomic regions that initiate transcription, and
enhancers are regulatory DNA elements that increase
the rate of transcription.
Enhancers are DNA sequences of several hundred
base pairs in length that contain binding sites for vari
ous transcription activator proteins. These elements
activate gene transcription, regardless of the position
relative to the gene promoter [1–3]. The enhancers
can be located at a distance of few hundred bp and up
to one million bp from the promoter . They can be
situated in the intergenic spacer regions and in the
transcribed regions (in introns or even exons of the
genes) [5, 6].
It is now known that most of the genome is tran
scribed and that a considerable part of transcripts,
and mammals, is represented by
long nonproteincoding RNAs (lncRNAs) [7–10].
The length of these transcripts ranges from several
hundred to several thousand base pairs [7–9, 11].
Recent data suggest an important role of at least some
lncRNAs in the transcriptional regulation of protein
coding mRNAs .
The existing experimental data suggest that lncRNAs
may be associated with both transcription activation
and repression of proteincoding genes . For
example, the presence of lncRNAs in the regulatory
region of the
correlates with the repressed state of this locus [14,
15]. For some mammal transcripts, an association
with the repression of their target genes was also dem
onstrated [16–21]. In particular, HOTAIR ncRNA is
required for repression of the HOXD locus . For
some negatively acting ncRNAs, interaction with the
PcG repressor proteins was demonstrated [16–20].
On the other hand, there are data pointing to a pos
itive role of lncRNAs in gene transcription. For exam
ple, it was shown that transcription through silencer
could counteract repression in model transgenic sys
tems . Some lncRNAs proved to have a positive
influence on the expression of neighboring genes .
Moreover, as a result of wholegenome analysis, the
lncRNAs associated with some enhancers (called
enhancer RNAs, or eRNAs) were identified. These
lncRNAs are transcribed near or directly within active
enhancers and can be spliced and polyadenylated.
However, the regulatory function of these RNAs
remains weakly studied [24–26]. It was demonstrated
that some lncRNAs could interact with activator pro
teins [27–29] and with the protein components of the
The Effect of Transcription on Enhancer Activity
M. M. Erokhin
, A. I. Davydova
, D. V. Lomaev
P. G. Georgiev
, and D. A. Chetverina
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia
email: email@example.com, firstname.lastname@example.org, email@example.com
LIA 1066, Laboratorie FrancoRusse de recherche en oncologie, Moscow, 119334 Russia
Received March 11, 2015
—In higher eukaryotes, the level of gene transcription is under the control of DNA regulatory ele
ments, such as promoter, from which transcription is initiated with the participation of RNA polymerase II
and general transcription factors, as well as the enhancer, which increase the rate of transcription with the
involvement of activator proteins and cofactors. It was demonstrated that enhancers are often located in the
transcribed regions of the genome. We showed earlier that transcription negatively affected the activity of
in model transgenic systems. In this study, we tested the effect of the distance
between the leading promoter, enhancer, and target promoter on the inhibitory effect of transcription of dif
ferent strength. It was demonstrated that the negative effect of transcription remained, but weakened with
increased distance between the leading promoter and enhancer and with decreased distance between the
enhancer and target promoter. Thus, transcription can modulate the activity of enhancers by controlling its
, enhancer, noncoding transcription, enhancer suppression, transgene