Main results

Genomics of cis-regulatory elements (L.G. Nikolaev, S.B. Akopov, I.P. Chernov, T.L. Azhikina)

Publication of nucleotide sequences of several eukaryotic genomes opened up a possibility to study the regulatory mechanisms determining the phenotypic variability of living organisms. Mammalian genome contains up to 30,000 protein-coding genes, and much larger portion of the genome is transcribed. Both genes and transcribed genome regions of a multicellular organism are participate in complex regulated network that determines the existence of many specialized cell types. Transcription of genes and non-coding sequences is regulated at several levels: linear genome architecture represented by DNA cis-regulatory elements, modifications of DNA, chromatin structure, compartmental organization of the nucleus etc.

Despite the achievements in a study of individual regulatory systems, we are still far away from complete understanding of the mechanisms that regulate the genome as a whole. Even in the relatively simple cases of cis-regulators identification we encounter serious problems which demand great efforts from many researchers to be solved. For example, it is predicted that human genome may contain up to 100,000 enhancers and silencers, but only small part of them is characterized to date.

A very important part of genome regulatory machinery are epigenetic elements, i.e. elements determining stably inherited changes in gene expression level without change of DNA sequence. Among them are sites of DNA methylation, regions containing modified histones etc. In mammals, methylation of CpG sites plays a key role in gene regulation by means of either modification of cis-regulatory elements or modification of long genome region which is associated with chromatin conformation change. To elucidate the mechanisms of methyl-dependent regulation of expression the detailed maps of methylation of long genomic regions are necessary. A comparison of these maps for different types of cells may reveal how DNA methylation affects gene expression.

In our lab several methods are developed allowing a high-throughput identification and genome mapping of non-methylated CpG dinucleotides, transcription start sites, and several genomic regulatory elements — nuclear matrix attachment sites (S/MARs), insulators, enhancers, open and closed chromatin regions, and binding sites of DNA-recognizing proteins including transcription factors, within long (1–2 megabases) DNA sequences. The data obtained are integrated within relatively small (1 megabase) region of human chromosome 19. Also, we construct maps of polygenic genome regions for normal and tumor tissues which are necessary for study of genome regulation and for practical use in medical genetics.

Structure and functional study of Mycobacterium tuberculosis, Burkholderia pseudomallei and Burkholderia mallei pathogenesis (T.L. Azhikina, G.S. Monastyrskaya)

Tuberculosis — a chronic infection caused by Gram-positive bacteria Mycobacterium tuberculosis — is one of ten world’s main causes of premature death and second among infections. Mycobacterial genome is extremely variable that complicates tuberculosis diagnostics and therapy. We developed the experimental method of comparative analysis of the genomes — the RFLP subtractive hybridization — which allows comparing genomes of closely related bacterial strains. With the use of this system a comparison of the genomes of different M. tuberculosis strains circulating in Russia and causing different clinical manifestations of the disease was performed. Basing on the differential sequences obtained the experimental approach was developed allowing to study an insertion-deletion polymorphism within Russian population of M. tuberculosis (ID-typing).

M. tuberculosis caused human infection with a wide spectrum of clinical manifestations that depends on complex and not completely studied interactions between host and bacterium. We are studying a full spectrum of transcripts of the M. tuberculosis genes during primary infection and after the transition into chronic and latent forms. This will help to reveal the hoe the pathogen escapes from host response. In collaboration with the immunogenetics lab of Central Institute for Tuberculosis (Head Prof. A.S. Apt) we developed a method allowing for analysis of the intracellular pathogen’s transcriptome directly in infected tissues. The method may be useful for search of virulence factors, targets for drug therapy and for development of the epidemiological monitoring strategy for any pathogen.

In collaboration with State Scientific Center of Applied Microbiology (I. Abaev) the whole-genome comparison of pathogenic Burkholderia pseudomallei C—141 and Burkholderia mallei C5 strains causing melioidosis and glanders was performed. The library was constructed that contains DNA fragment that differs between B. pseudomallei C141 and B. mallei C5 and maybe used for diagnostics of melioidosis and glanders.

Approaches to diagnostics and gene therapy of cancer (T.V. Vinogradova, E.P. Kopantzev, I.P. Chernov)

Currently much attention is paid to development of new generation therapy of cancer. Within the framework of the State program «Priority fields in science and technology in Russia during 2007–2012» our lab participated in the integrated project «Development and production of the prototype of novel and effective therapies and diagnostics of the post-genome generation for use in tumor therapy». The aim of this project was the development and clinical tests of first gene therapy based preparations for treatment of lung and esophagus cancers. The approaches used in this project are based on the fundamental and methodical research performed in the laboratory. The project integrates efforts of the major scientific centers of Russia: Institute of Molecular genetics RAS, Blokhin Cancer Research Center RAMS, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Novosibirsk State University, Institute of gene biology RAS, Gamaleya Research Institute of Epidemiology and Microbiology RAMS, and biotechnology companies Evrogen and Binnofarm. Within the framework of this project the constructions allowing for specific expression of therapeutic genes in tumor cells and systems for delivery of the therapeutic genes into tumors were developed.

Hence, the bases were established for the development and production of novel effective medical preparations and diagnostics based on gene therapy approach and biologically active proteins.

Cancer and development (M.V. Zinovyeva, T.V. Vinogradova, G.S. Monastyrskaya)

Demonstration of the fact that genes that are activated during development of lung and esophagus in embryogenesis are switched off in normal cells when they are being transformed into cancer cells and conversely is one the major achievements of the project. This confirms the hypothesis that process of cancer transformation and progression of normal cells may be compared with embryonal development or self-reproduction and differentiation of stem cells of certain tissues. The genes that express differentially in cancer and development probably play key role in tumorigenesis. Study of such genes allows carrying out a rational choice of therapeutic targets because systems regulating embryonal development and damaged in cancer are most perspective targets.

Modified oligonucleotides (V.K. Potapov)

Development of new methods of production and synthesis of modified oligonucleotides with changed structure of the base or of sugar-phosphate skeleton was the mainstream of the group through the last three years. Working out of approaches to solid phase synthesis of morpholino-analogues of oligonucleotides, which have morpholine ring in their structure instead of ribose, is the most perspective direction of the research. Such analogues are uncharged molecules and resistant to nucleases. They preserve DNA structure and form stable complementary bonds with native oligonucleotides.

Synthesis of oligonucleotides bearing spacers of specified length with thiol group in certain sites is the second direction of the work. These oligonucleotides are used in study of their complexes with integrases of HIV and ASV by X-ray diffraction analysis by prof. Vlodover group (NCI, Frederic).

Name	Position	E-mail
Sergej B. Akopov, ph. d.	s. r. f.	akser@ibch.ru
Ljudmila V. Averina	eng.
Tatyana L. Azhikina, d. sc.	s. r. f.	tatazhik@ibch.ru
Nina N. Beljaeva, ph. d.	r. f.
. Biltueva	PhD stud.	bjuliya87@mail.ru
Irina V. Boni, ph. d.	s. r. f.	irina_boni@ibch.ru
Svetlana S. Bulanenkova, ph. d.	r. f.
Igor' P. Chernov, ph. d.	r. f.	igor_ch@ibch.ru
Dmitry . Didych, ph. d.	r. f.	dmitry_d@inbox.ru
Ol'ga B. Filjukova, ph. d.	r. f.
Kirill N. Kashkin, ph. d.	r. f.
Ljudmila S. Koledinskaja	j. r. f.
Evgenij P. Kopancev, ph. d.	s. r. f.	kopantzev@ibch.ru
Zoja B. Kravchenko	res. eng.
Tat'jana L. Levitan	res. eng.	levitanibh@mail.ru
Natalija I. Medvedeva	res. eng.
Galina S. Monastyrskaya, ph. d., senior research associate	l. r. f.	gal@ibch.ru
Lev G. Nikolaev, d. sc.	s. r. f.	lev@ibch.ru
Oxana Y. Ovchinnikova, ph. d.		ovchox@gmail.com
Rudolf A. Pogosyan	j. r. f.	r.j.f@mail.ru
Viktor K. Potapov, d. sc.	l. r. f.	vk@ibch.ru
Aleksandr V. Sass	j. r. f.
Nadezhda V. Skapcova	r. f.
Timofey A. Skvortsov, ph. d.	r. f.	timofey@ibch.ru
Evgeny V. Snezhkov, ph. d.	s. r. f.	eugene@ibch.ru
Nataliya Y. Uspenskaya, ph. d.	s. r. f.	usp@ibch.ru
Tat'jana V. Vinogradova, ph. d.	s. r. f.	tv@ibch.ru
Ljudmila L. Zavalova, ph. d.	s. r. f.	lz@ibch.ru
Marina V. Zinov'eva, ph. d.	r. f.	mzinov@ibch.ru

Selected publications

1. Kopantzev E.P., Monastyrskaya G.S., Vinogradova T.V., Zinovyeva M.V., Kostina M.B., Filyukova O.B., Tonevitsky A.G., Sukhikh G.T., Sverdlov E.D. (2008). Differences in gene expression levels between early and later stages of human lung development are opposite to those between normal lung tissue and non-small lung cell carcinoma. Lung Cancer 62 (1), 23–34 [+]

   We, for the first time, directly compared gene expression profiles in human non-small cell lung carcinomas (NSCLCs) and in human fetal lung development. Previously reported correlations of gene expression profiles between lung cancer and lung development, deduced from matching data on mouse development and human cancer, have brought important information, but suffered from different timing of mouse and human gene expression during fetal development and fundamental differences in tumorigenesis in mice and humans. We used the suppression subtractive hybridization technique to subtract cDNAs prepared from human fetal lung samples at weeks 10-12 and 22-24 and obtained a cDNA library enriched in the transcripts more abundant at the later stage. cDNAs sequencing and RT-PCR analysis of RNAs from human fetal and adult lungs revealed 12 differentially transcribed genes: ADH1B, AQP1, FOLR1, SLC34A2, CAV1, INMT, TXNIP, TPM4, ICAM-1, HLA-DRA, EFNA1 and HLA-E. Most of these genes were found up-regulated in mice and rats at later stages than in human lung development. In surgical samples of NSCLC, these genes were down-regulated as compared to surrounding normal tissues and normal lungs, thus demonstrating opposite expression profiles for the genes up-regulated during fetal lung development.

2. Chernov I.P., Timchenko K.A., Akopov S.B., Nikolaev L.G., Sverdlov E.D. (2007). Identification of tissue-specific DNA-protein binding sites by means of two-dimensional electrophoretic mobility shift assay display. Anal. Biochem. 364 (1), 60–6 [+]

   We developed a technique of differential electrophoretic mobility shift assay (EMSA) display allowing identification of tissue-specific protein-binding sites within long genomic sequences. Using this approach, we identified 10 cell type-specific protein-binding sites (protein target sites [PTSs]) within a 137-kb human chromosome 19 region. In general, tissue-specific binding of proteins from different nuclear extracts by individual PTSs did not follow the all-or-nothing principle. Most often, PTS-protein complexes were formed in all cases, but they were different for different nuclear extracts used.

3. Bulanenkova S., Snezhkov E., Nikolaev L., Sverdlov E. (2007). Identification and mapping of open chromatin regions within a 140 kb polygenic locus of human chromosome 19 using E. coli Dam methylase. Genetica 130 (1), 83–92 [+]

   Using transient expression of the E. coli Dam methylase gene and analysis of the distribution of methylated GATC sites, we studied the distribution of open chromatin regions within a 140 kb long human genome segment in HEK-293 cells. Dam methylated sites were found in gene introns, exons, and intergenic regions, and their distribution along DNA was uneven. There were regions of high and low density of Dam methylated GATC sites, presumably corresponding to "open" and "closed" chromatin regions, respectively, and to the functional profile of the genomic locus under study. The Dam methylation profile was also generally in agreement with transcriptional activity of genes in the locus. Moreover, DNA regions accessible to Dam methylase apparently coincided with those hypersensitive to DNase I.

4. Illarionova A.E., Vinogradova T.V., Sverdlov E.D. (2007). Only those genes of the KIAA1245 gene subfamily that contain HERV(K) LTRs in their introns are transcriptionally active. Virology 358 (1), 39–47 [+]

   Insertion of LTRs into some genome locations might seriously affect regulation of the neighboring genes expression. This hypothesis is widely accepted but, however, not confirmed directly. Earlier, we have identified a family of closely related genes highly similar to the KIAA1245 mRNA counterpart. This family included a subfamily of genes some of which contained and the others lacked an LTR in their structure. We compared transcription of several closely related genes of the subfamily differing in the presence or absence of LTRs. Only LTR-containing genes were transcribed in transformed cell lines, tumorous and embryonic human tissues, whereas LTR-lacking genes remained silent. Since the genes were in the same intracellular microenvironment, we suggested that this effect was most probably due to intrinsic cis-characteristics of integrated LTRs and confirmed this by demonstrating high enhancer activity of KIAA1245 LTRs. The expression of the LTR-containing genes in embryonic tissues might suggest their involvement in evolutionary events during primate speciation.

5. Buzdin A., Kovalskaya-Alexandrova E., Gogvadze E., Sverdlov E. (2006). At least 50% of human-specific HERV-K (HML-2) long terminal repeats serve in vivo as active promoters for host nonrepetitive DNA transcription. J. Virol. 80 (21), 10752–62 [+]

   We report the first genome-wide comparison of in vivo promoter activities of a group of human-specific endogenous retroviruses in healthy and cancerous germ line tissues. To this end, we employed a recently developed technique termed genomic repeat expression monitoring. We found that at least 50% of human-specific long terminal repeats (LTRs) possessed promoter activity, and many of them were up- or downregulated in a seminoma. Individual LTRs were expressed at markedly different levels, ranging from approximately 0.001 to approximately 3% of the housekeeping beta-actin gene transcript level. We demonstrated that the main factors affecting the LTR promoter activity were the LTR type (5'-proviral, 3' proviral, or solitary) and position with regard to genes. The averaged promoter strengths of solitary and 3'-proviral LTRs were almost identical in both tissues, whereas 5'-proviral LTRs displayed two- to fivefold higher promoter activities. The relative content of promoter-active LTRs in gene-rich regions was significantly higher than that in gene-poor loci. This content was maximal in those regions where LTRs "overlapped" readthrough transcripts. Although many promoter-active LTRs were mapped near known genes, no clear-cut correlation was observed between transcriptional activities of genes and neighboring LTRs. Our data also suggest a selective suppression of transcription for LTRs located in gene introns.

6. Akopov S.B., Ruda V.M., Batrak V.V., Vetchinova A.S., Chernov I.P., Nikolaev L.G., Bode J., Sverdlov E.D. (2006). Identification, genome mapping, and CTCF binding of potential insulators within the FXYD5-COX7A1 locus of human chromosome 19q13.12. Mamm. Genome 17 (10), 1042–9 [+]

   Identification of insulators is one of the most difficult problems in functional mapping of genomes. For this reason, up to now only a few insulators have been described. In this article we suggest an approach that allows direct isolation of insulators by a simple positive-negative selection based on blocking enhancer effects by insulators. The approach allows selection of fragments capable of blocking enhancers from mixtures of genomic fragments prepared from up to 1-Mb genomic regions. Using this approach, a 1-Mb human genome locus was analyzed and eight potential insulators were selected. Five of the eight sequences were positioned in intergenic regions and two were within introns. The genes of the alpha-polypeptide H+/K+ exchanging ATPase (ATP4A) and amyloid beta (A4) precursor-like protein 1 (APLP1) within the locus studied were found to be flanked by insulators on both sides. Both genes are characterized by distinct tissue-specific expression that differs from the tissue specificity of the surrounding genes. The data obtained are consistent with the conception that insulators subdivide genomic DNA into loop domains that comprise genes characterized by similar expression profiles. Using chromatin immunoprecipitation assay, we demonstrated also that at least six of the putative insulators revealed in this work could bind the CTCF transcription factor in vivo. We believe that the proposed approach could be a useful instrument for functional analysis of genomes.

7. Fushan A., Monastyrskaya G., Abaev I., Sverdlov E. (2006). Genomic fingerprinting of Burkholderia pseudomallei and B. mallei pathogens with DNA array based on interspecies sequence differences obtained by subtractive hybridization. Res. Microbiol. 157 (7), 684–92 [+]

   The ability to rapidly and efficiently identify causative agents of dangerous human and animal diseases is a prerequisite to diagnosis, prophylaxis and therapy. Such identification systems can be developed based on DNA markers enabling differentiation between various bacterial strains. One source of these markers is genetic polymorphism. An efficient method for detecting the most stable polymorphisms without knowledge of genomic sequences is subtractive hybridization. In this work we report an approach to typing of Burkholderia pseudomallei and B. mallei that cause melioidosis and glanders, respectively. Typing is based on hybridization of bacterial genomes with a DNA array of genomic markers obtained using subtractive hybridization. The array comprised 55 DNA fragments which distinguished the genomes of B. pseudomallei C-141 and B. mallei C-5 strains, and it was used to test 28 radioactively labeled B. pseudomallei strains and 8 B. mallei strains. Each strain was characterized by a specific hybridization pattern, and the results were analyzed using cluster analysis. 18 patterns specific to B. pseudomallei and 6 patterns specific to B. mallei were found to be unique. The data allowed us to differentiate most studied B. pseudomallei variants from one another and from B. mallei strains. It was concluded that DNA markers obtained by subtractive hybridization can be potentially useful for molecular typing of B. pseudomallei and B. mallei strains, as well as for their molecular diagnosis. The method reported can be easily adapted for use both with DNA arrays and DNA microarrays with fluorescent probes.

8. Vetchinova A.S., Akopov S.B., Chernov I.P., Nikolaev L.G., Sverdlov E.D. (2006). Two-dimensional electrophoretic mobility shift assay: identification and mapping of transcription factor CTCF target sequences within an FXYD5-COX7A1 region of human chromosome 19. Anal. Biochem. 354 (1), 85–93 [+]

   An approach for fast identification and mapping of transcription factor binding sites within long genomic sequences is proposed. Using this approach, 10 CCCTC-binding factor (CTCF) binding sites were identified within a 1-Mb FXYD5-COX7A1 human chromosome 19 region. In vivo binding of CTCF to these sites was verified by chromatin immunoprecipitation assay. CTCF binding sites were mapped within gene introns and intergenic regions, and some of them contained Alu-like repeated elements.

9. Azhikina T., Gainetdinov I., Skvortsova Y., Sverdlov E. (2006). Methylation-free site patterns along a 1-Mb locus on Chr19 in cancerous and normal cells are similar. A new fast approach for analyzing unmethylated CCGG sites distribution. Mol. Genet. Genomics 275 (6), 615–22 [+]

   We describe a newly developed technique for rapid identification of positions of genomic DNA breaks, preexisting or introduced by specific digestion, in particular, by restriction endonucleases (RIDGES). We applied RIDGES in analyzing unmethylated CCGG sites distribution along a 1-Mb long genome region (D19S208-COX7A1 on chromosome 19) in cancerous and normal lung tissues. Both tissues were characterized by a profoundly uneven density of unmethylated sites along the fragment. Interestingly, the distribution of hypomethylated regions did not correlate with gene locations within the fragment, and one of the most hypomethylated areas contained practically no genes. We also demonstrated that the methylation pattern of a long genome DNA fragment was rather stable and practically unchanged in human lung cancer tissue as compared with its normal counterpart, in accordance with the suggestion (Ross et al. in Nat Genet 24:227-235, 2000) that cell lines of common origin have typically similar transcription profiles. An analogous suggestion might probably be made for global methylation patterns of genomic DNA.

10. Azhikina T., Gvozdevsky N., Botvinnik A., Fushan A., Shemyakin I., Stepanshina V., Lipin M., Barry C. 3rd, Sverdlov E. (2006). A genome-wide sequence-independent comparative analysis of insertion-deletion polymorphisms in multiple Mycobacterium tuberculosis strains. Res. Microbiol. 157 (3), 282–90 [+]

    We applied an enhanced version of subtractive hybridization for comparative analyses of indel differences between genomes of several Mycobacterium tuberculosis strains widespread in Russian regions, and the H37Rv reference strain. A number of differences were detected and partially analyzed, thus demonstrating the practicality of the approach. A majority of the insertions found were shared by all Russian strains, except for strain 1540 that revealed the highest virulence in animal tests. This strain possesses a number of genes absent from other clinical strains. Two of the differential genes were found to encode putative membrane proteins and are presumed to affect mycobacterial interaction with the host cell, thus enhancing virulent properties of the isolate. The method used is of general application, and enables the elaboration of a catalogue of indel polymorphic genomic differences between closely related strains.

11. Kovalskaya E., Buzdin A., Gogvadze E., Vinogradova T., Sverdlov E. (2006). Functional human endogenous retroviral LTR transcription start sites are located between the R and U5 regions. Virology 346 (2), 373–8 [+]

    Human endogenous retroviruses (HERVs) occupy about 5% of human DNA and are thought to be remnants of ancient retroviral infections of human ancestors' germ cells. HERVs can modify expression of host cell genes through their cis-regulatory elements concentrated in their long terminal repeats (LTRs). Although numerous HERV-related RNAs were identified in the human transcriptome, for most of them, it remains unclear whether they are LTR-promoted or read-through products initiated from neighboring genomic promoters. Here, we describe mapping of transcriptional start sites within solitary and proviral LTRs of the HERV-K (HML-2) human-specific subfamily of endogenous retroviruses. Surprisingly, the transcription was initiated predominantly from the very 3' termini of the LTR R regions. The data presented here may shed light on adaptive coevolution of human endogenous retroviruses with their host cells.

12. Buzdin A., Kovalskaya-Alexandrova E., Gogvadze E., Sverdlov E. (2006). GREM, a technique for genome-wide isolation and quantitative analysis of promoter active repeats. Nucleic Acids Res. 34 (9), e67 [+]

    We developed a technique called GREM (Genomic Repeat Expression Monitor) that can be applied to genome-wide isolation and quantitative analysis of any kind of transcriptionally active repetitive elements. Briefly, the technique includes three major stages: (i) generation of a transcriptome wide library of cDNA 5' terminal fragments, (ii) selective amplification of repeat-flanking genomic loci and (iii) hybridization of the cDNA library (i) to the amplicon (ii) with subsequent selective amplification and cloning of the cDNA-genome hybrids. The sequences obtained serve as 'tags' for promoter active repetitive elements. The advantage of GREM is an unambiguous mapping of individual promoter active repeats at a genome-wide level. We applied GREM for genome-wide experimental identification of human-specific endogenous retroviruses and their solitary long terminal repeats (LTRs) acting in vivo as promoters. Importantly, GREM tag frequencies linearly correlated with the corresponding LTR-driven transcript levels found using RT-PCR. The GREM technique enabled us to identify 54 new functional human promoters created by retroviral LTRs.

13. Mamedov I., Batrak A., Buzdin A., Arzumanyan E., Lebedev Y., Sverdlov E.D. (2002). Genome-wide comparison of differences in the integration sites of interspersed repeats between closely related genomes. Nucleic Acids Res. 30 (14), e71 [+]

    New whole-genome approach to comparison of LTR distribution in genomes of related species was presented. The eleven LTR insertions distinguishing human genome from chimpanzee ones were described at the first time.

14. Buzdin A., Khodosevich K., Mamedov I., Vinogradova T., Lebedev Y., Hunsmann G., Sverdlov E. (2002). A technique for genome-wide identification of differences in the interspersed repeats integrations between closely related genomes and its application to detection of human-specific integrations of HERV-K LTRs. Genomics 79 (3), 413–22 [+]

    We have developed a method of targeted genomic difference analysis (TGDA) for genomewide detection of interspersed repeat integration site differences between closely related genomes. The method includes a whole-genome amplification of the flanks adjacent to target interspersed repetitive elements in both genomic DNAs under comparison, and subtractive hybridization (SH) of the selected amplicons. The potential of TGDA was demonstrated by the detection of differences in the integration sites of human endogenous retroviruses K (HERV-K) and related solitary long terminal repeats (LTRs) between the human and chimpanzee genomes. Of 55 randomly sequenced clones from a library enriched with human-specific integration (HSI) sites, 33 (60%) represented HSIs. All the human-specific (Hs) LTRs belong to two related evolutionarily young groups, suggesting simultaneous activity of two master genes in the hominid lineage. No deletion/insertion polymorphism was detected for the LTR HSIs for 25 unrelated caucasoid individuals. We also discuss the possible research applications for TGDA research.

15. Sverdlov E.D. (2000). Retroviruses and primate evolution. BioEssays 22 (2), 161–171 [+]

    Human endogenous retroviruses (HERVs), probably representing footprints of ancient germ-cell retroviral infections, occupy about 1% of the human genome. HERVs can influence genome regulation through expression of retroviral genes, either via genomic rearrangements following HERV integrations or through the involvement of HERV LTRs in the regulation of gene expression. Some HERVs emerged in the genome over 30 MYr ago, while others have appeared rather recently, at about the time of hominid and ape lineages divergence. HERVs might have conferred antiviral resistance on early human ancestors, thus helping them to survive. Furthermore, newly integrated HERVs could have changed the pattern of gene expression and therefore played a significant role in the evolution and divergence of Hominoidea superfamily. Comparative analysis of HERVs, HERV LTRs, neighboring genes, and their regulatory interplay in the human and ape genomes will help us to understand the possible impact of HERVs on evolution and genome regulation in the primates.

Head of the laboratory

Eugeny Sverdlov

• Russia, Moscow, Ul. Miklukho-Maklaya 16/10 — On the map
• IBCh RAS, build. 52, office 657
• Phone: +7 (495) 330-65-29
• E-mail: sverd@ibch.ru

Administrative assistant

Levitan Tatyana Lvovna

• Phone: +7 (495) 330-65-29
• Fax: +7 (495) 330-65-38
• E-mail: sverd@humgen.siobc.ras.ru; levitanibh@mail.ru