Ilya Ioshikhes

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Ilya Ioshikhes
Associate Professor

Room: Roger Guindon Hall, room 4209 (office), 4208 (lab)
Office: 613-562-5800 ext. 4882
Work E-mail: iioschik@uottawa.ca

Dr. Ilya Ioshikhes

Biography

Our research is focused on gene regulation. It includes several related projects and studies on chromatin, transcription factor (TF) interactions with DNA, promoter analysis and microRNAs. Specific projects include algorithms for mapping TF binding sites and cis-regulatory modules, nucleosome mapping, the study of the influence of histone variants on chromatin architecture, chromatin modeling, and the development of algorithms for mapping miRNA targets. Other areas of bioinformatics, such as the human milk metagenome, are also part of our area of interest. Our goal is the mathematical modeling of gene regulation processes on various levels, combined with position prediction of regulatory elements.

Research Program

The study of the regulation of gene expression is a fundamental problem in molecular biology. Transcriptional regulation is maintained through the interactions of various transcription factors (TFs) with the protein components of base transcriptional complexes. The DNA sequences of the promoters, enhancers and other regulatory regions of the genes contain specific binding sites for transcription factors and other components of the transcription machinery. These sites serve as a scaffold to bring various TFs into close proximity to each other to facilitate their interaction and form active DNA-protein regulation complexes. In our research, we focus on the investigation of interactions between promoters and transcription factor complexes and the discovery of gene regulatory modules in the proximal promoter sequences and long gene regulatory regions.

To be properly understood, promoter machinery must be studied within its chromatin context. Current and planned directions of our research in this area include the refinement of nucleosome sequence patterns in new experimental data; a comparative analysis of common nucleosomes and those with histone modifications (H2A.Z, CENP-A and others); the analysis of species-specific and tissue-specific chromatin structures; an analysis of the relationship between specific mechanisms of chromatin remodelling and alternative types of chromatin architecture; and an analysis of the interaction of nucleosomes with TFs and other regulatory elements. Our research also includes algorithm development for mapping microRNA targets, the study of the human milk metagenome and other projects.


Selected Publications

  • Pranckeviciene E, Hosid S, Liang N, Ioshikhes I. Nucleosome positioning sequence patterns as packing or regulatory. PLoS Comput Biol. 2020 Jan 27;16(1):e1007365. doi: 10.1371/journal.pcbi.1007365. eCollection 2020 Jan. PubMed PMID: 31986131; PubMed Central PMCID: PMC7004410.
  • Mahmud AKMF, Yang D, Stenberg P, Ioshikhes I, Nandi S. Exploring a Drosophila Transcription Factor Interaction Network to Identify Cis-Regulatory Modules. J Comput Biol. 2019 Dec 20. doi: 10.1089/cmb.2018.0160. [Epub ahead of print] PubMed PMID: 31855461.
  • Alvarez-Saavedra M, Yan K, De Repentigny Y, Hashem LE, Chaudary N, Sarwar S, Yang D, Ioshikhes I, Kothary R, Hirayama T, Yagi T, Picketts DJ. Snf2h Drives Chromatin Remodeling to Prime Upper Layer Cortical Neuron Development. Front Mol Neurosci. 2019 Oct 17;12:243. doi: 10.3389/fnmol.2019.00243. eCollection 2019. PubMed PMID: 31680852; PubMed Central PMCID: PMC6811508.
  • Hamed M, Khilji S, Dixon K, Blais A, Ioshikhes I, Chen J, Li Q. Insights into interplay between rexinoid signaling and myogenic regulatory actor-associated chromatin state in myogenic differentiation. Nucleic Acids Res. 2017 Nov 2;45(19):11236-11248. doi: 10.1093/nar/gkx800. PubMed PMID: 28981706; PubMed Central PMCID: PMC5737385.
  • Yang D, Ioshikhes I. Drosophila H2A and H2A.Z Nucleosome Sequences Reveal Different Nucleosome Positioning Sequence Patterns. J Comput Biol. 2017 Apr;24(4):289-298. doi: 10.1089/cmb.2016.0173. Epub 2016 Dec 19. PubMed PMID: 27992255.
  • Rajagopalan M, Balasubramanian S, Ioshikhes I, Ramaswamy A. Structural dynamics of nucleosome mediated by acetylations at H3K56 and H3K115,122. Eur Biophys J. 2017 Jul;46(5):471-484. doi: 10.1007/s00249-016-1191-5. Epub 2016 Dec 8. PubMed PMID: 27933430.
  • Alvarez-Saavedra M, De Repentigny Y, Yang D, O'Meara RW, Yan K, Hashem LE, Racacho L, Ioshikhes I, Bulman DE, Parks RJ, Kothary R, Picketts DJ. Voluntary Running Triggers VGF-Mediated Oligodendrogenesis to Prolong the Lifespan of Snf2h-Null Ataxic Mice. Cell Rep. 2016 Oct 11;17(3):862-875. doi: 10.1016/j.celrep.2016.09.030. PubMed PMID: 27732860.
  • Wight A, Yang D, Ioshikhes I, Makrigiannis AP. Nucleosome Presence at AML-1 Binding Sites Inversely Correlates with Ly49 Expression: Revelations from an Informatics Analysis of Nucleosomes and Immune Cell Transcription Factors. PLoS Comput Biol. 2016 Apr 28;12(4):e1004894. doi: 10.1371/journal.pcbi.1004894. eCollection 2016 Apr. PubMed PMID: 27124577; PubMed Central PMCID: PMC4849748.
  • Hosid S, Ioshikhes I. Apoptotic lymphocytes of H. sapiens lose nucleosomes in GC-rich promoters. PLoS Comput Biol. 2014 Jul 31;10(7):e1003760. doi: 10.1371/journal.pcbi.1003760. eCollection 2014 Jul. PubMed PMID: 25077608; PubMed Central PMCID: PMC4117428.
  • Alvarez-Saavedra M, De Repentigny Y, Lagali PS, Raghu Ram EV, Yan K, Hashem E, Ivanochko D, Huh MS, Yang D, Mears AJ, Todd MA, Corcoran CP, Bassett EA,Tokarew NJ, Kokavec J, Majumder R, Ioshikhes I, Wallace VA, Kothary R, Meshorer E, Stopka T, Skoultchi AI, Picketts DJ. Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation. Nat Commun. 2014 Jun 20;5:4181. doi: 10.1038/ncomms5181. PubMed PMID: 24946904; PubMed Central PMCID: PMC4083431.
  • Morozov VY, Ioshikhes IP. Optimized position weight matrices in prediction of novel putative binding sites for transcription factors in the Drosophila melanogaster genome. PLoS One. 2013 Aug 6;8(8):e68712. doi: 10.1371/journal.pone.0068712. Print 2013. PubMed PMID: 23936309; PubMed Central PMCID: PMC3735551.
  • Nandi S, Blais A, Ioshikhes I. Identification of cis-regulatory modules in promoters of human genes exploiting mutual positioning of transcription factors. Nucleic Acids Res. 2013 Oct;41(19):8822-41. doi: 10.1093/nar/gkt578. Epub 2013 Aug 2. PubMed PMID: 23913413; PubMed Central PMCID: PMC3799424.
  • Ward TL, Hosid S, Ioshikhes I, Altosaar I. Human milk metagenome: a functional capacity analysis. BMC Microbiol. 2013 May 25;13:116. doi:10.1186/1471-2180-13-116. PubMed PMID: 23705844; PubMed Central PMCID: PMC3679945.
  • Ramaswamy A, Ioshikhes I. Dynamics of modeled oligonucleosomes and the role of histone variant proteins in nucleosome organization. Adv Protein Chem Struct Biol. 2013;90:119-49. doi: 10.1016/B978-0-12-410523-2.00004-3. PubMed PMID: 23582203.
  • Nandi S, Ioshikhes I. Optimizing the GATA-3 position weight matrix to improve the identification of novel binding sites. BMC Genomics. 2012 Aug 22;13:416. doi: 10.1186/1471-2164-13-416. PubMed PMID: 22913572; PubMed Central PMCID: PMC3481455.
  • Liu Y, Nandi S, Martel A, Antoun A, Ioshikhes I, Blais A. Discovery, optimization and validation of an optimal DNA-binding sequence for the Six1 homeodomain transcription factor. Nucleic Acids Res. 2012 Sep 1;40(17):8227-39. Epub 2012 Jun 22. PubMed PMID: 22730291; PubMed Central PMCID: PMC3458543.
  • Ioshikhes I, Hosid S, Pugh BF. Variety of genomic DNA patterns for nucleosome positioning. Genome Res. 2011 Nov;21(11):1863-71. doi: 10.1101/gr.116228.110. Epub 2011 Jul 12. PubMed PMID: 21750105; PubMed Central PMCID: PMC3205571.
  • Kaminsky Z, Tochigi M, Jia P, Pal M, Mill J, Kwan A, Ioshikhes I, Vincent JB, Kennedy JL, Strauss J, Pai S, Wang SC, Petronis A. A multi-tissue analysis identifies HLA complex group 9 gene methylation differences in bipolar disorder. Mol Psychiatry. 2012 Jul;17(7):728-40. doi: 10.1038/mp.2011.64. Epub 2011 Jun 7. PubMed PMID: 21647149.
  • Mavrich TN, Ioshikhes IP, Venters BJ, Jiang C, Tomsho LP, Qi J, Schuster SC, Albert I, Pugh BF. A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res. 2008 Jul;18(7):1073-83. doi: 10.1101/gr.078261.108. Epub 2008 Jun 12. PubMed PMID: 18550805; PubMed Central PMCID: PMC2493396.
  • Mavrich TN, Jiang C, Ioshikhes IP, Li X, Venters BJ, Zanton SJ, Tomsho LP, Qi J, Glaser RL, Schuster SC, Gilmour DS, Albert I, Pugh BF. Nucleosome organization in the Drosophila genome. Nature. 2008 May 15;453(7193):358-62. doi: 10.1038/nature06929. Epub 2008 Apr 13. PubMed PMID: 18408708; PubMed Central PMCID: PMC2735122.
  • Smiraglia DJ, Kazhiyur-Mannar R, Oakes CC, Wu YZ, Liang P, Ansari T, Su J, Rush LJ, Smith LT, Yu L, Liu C, Dai Z, Chen SS, Wang SH, Costello J, Ioshikhes I, Dawson DW, Hong JS, Teitell MA, Szafranek A, Camoriano M, Song F, Elliott R, Held W, Trasler JM, Plass C, Wenger R. Restriction landmark genomic scanning (RLGS) spot identification by second generation virtual RLGS in multiple genomes with multiple enzyme combinations. BMC Genomics. 2007 Nov 30;8:446. PubMed PMID: 18053125; PubMed Central PMCID: PMC2235865.
  • Ramaswamy A, Ioshikhes I. Global dynamics of newly constructed oligonucleosomes of conventional and variant H2A.Z histone. BMC Struct Biol. 2007 Nov 8;7:76. PubMed PMID: 17996059; PubMed Central PMCID: PMC2216022.
  • Ioshikhes I, Roy S, Sen CK. Algorithms for mapping of mRNA targets for microRNA. DNA Cell Biol. 2007 Apr;26(4):265-72. Review. PubMed PMID: 17465893.
  • Ioshikhes IP, Albert I, Zanton SJ, Pugh BF. Nucleosome positions predicted through comparative genomics. Nat Genet. 2006 Oct;38(10):1210-5. Epub 2006 Sep 10. PubMed PMID: 16964265.
  • Gershenzon NI, Trifonov EN, Ioshikhes IP. The features of Drosophila core promoters revealed by statistical analysis. BMC Genomics. 2006 Jun 21;7:161. PubMed PMID: 16790048; PubMed Central PMCID: PMC1538597.
  • Gershenzon NI, Ioshikhes IP. Promoter classifier: software package for promoter database analysis. Appl Bioinformatics. 2005;4(3):205-9. PubMed PMID: 16231962.
  • Lee DH, Gershenzon N, Gupta M, Ioshikhes IP, Reinberg D, Lewis BA. Functional characterization of core promoter elements: the downstream core element is recognized by TAF1. Mol Cell Biol. 2005 Nov;25(21):9674-86. Erratum in: Mol Cell Biol. 2005 Dec;25(24):11192. PubMed PMID: 16227614; PubMed Central PMCID: PMC1265815.
  • Gershenzon NI, Stormo GD, Ioshikhes IP. Computational technique for improvement of the position-weight matrices for the DNA/protein binding sites. Nucleic Acids Res. 2005 Apr 22;33(7):2290-301. Print 2005. PubMed PMID: 15849315; PubMed Central PMCID: PMC1084321.
  • Ramaswamy A, Bahar I, Ioshikhes I. Structural dynamics of nucleosome core particle: comparison with nucleosomes containing histone variants. Proteins. 2005 Feb 15;58(3):683-96. PubMed PMID: 15624215.
  • Gershenzon NI, Ioshikhes IP. Synergy of human Pol II core promoter elements revealed by statistical sequence analysis. Bioinformatics. 2005 Apr 15;21(8):1295-300. Epub 2004 Nov 30. PubMed PMID: 15572469.
  • Babcock M, Pavlicek A, Spiteri E, Kashork CD, Ioshikhes I, Shaffer LG, Jurka J, Morrow BE. Shuffling of genes within low-copy repeats on 22q11 (LCR22) by Alu-mediated recombination events during evolution. Genome Res. 2003 Dec;13(12):2519-32. PubMed PMID: 14656960; PubMed Central PMCID: PMC403794.
  • Montgomery KT, Lee E, Miller A, Lau S, Shim C, Decker J, Chiu D, Emerling S, Sekhon M, Kim R, Lenz J, Han J, Ioshikhes I, Renault B, Marondel I, Yoon SJ, Song K, Murty VV, Scherer S, Yonescu R, Kirsch IR, Ried T, McPherson J, Gibbs R, Kucherlapati R. A high-resolution map of human chromosome 12. Nature. 2001 Feb 15;409(6822):945-6. PubMed PMID: 11237017.
  • Ioshikhes IP, Zhang MQ. Large-scale human promoter mapping using CpG islands. Nat Genet. 2000 Sep;26(1):61-3. PubMed PMID: 10973249.
  • Ioshikhes I, Trifonov EN, Zhang MQ. Periodical distribution of transcription factor sites in promoter regions and connection with chromatin structure. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2891-5. PubMed PMID: 10077607; PubMed Central PMCID: PMC15865.
  • Lvovsky L, Ioshikhes I, Raja MC, Zevin-Sonkin D, Sobolev IA, Liberzon A, Shwartzburd J, Ulanovsky LE. Interdependence between DNA template secondary structure and priming efficiencies of short primers. Nucleic Acids Res. 1998 Dec 1;26(23):5525-32. PubMed PMID: 9826780; PubMed Central PMCID: PMC148000.
  • Bolshoy A, Shapiro K, Trifonov EN, Ioshikhes I. Enhancement of the nucleosomal pattern in sequences of lower complexity. Nucleic Acids Res. 1997 Aug 15;25(16):3248-54. PubMed PMID: 9241237; PubMed Central PMCID: PMC146871.
  • Bolshoy A, Ioshikhes I, Trifonov EN. Applicability of the multiple alignment algorithm for detection of weak patterns: periodically distributed DNA pattern as a study case. Comput Appl Biosci. 1996 Oct;12(5):383-9. PubMed PMID: 8996786.
  • Ioshikhes I, Bolshoy A, Derenshteyn K, Borodovsky M, Trifonov EN. Nucleosome DNA sequence pattern revealed by multiple alignment of experimentally mapped sequences. J Mol Biol. 1996 Sep 20;262(2):129-39. Review. PubMed PMID: 8831784.
  • Ioshikhes I, Trifonov EN. Nucleosomal DNA sequence database. Nucleic Acids Res. 1993 Oct 25;21(21):4857-9. PubMed PMID: 8177730; PubMed Central PMCID: PMC311396.
  • Ioshikhes I, Bolshoy A, Trifonov EN. Preferred positions of AA and TT dinucleotides in aligned nucleosomal DNA sequences. J Biomol Struct Dyn. 1992 Jun;9(6):1111-7. PubMed PMID: 1637505.


 

Fields of Interest

  • Computational biology
  • Bioinformatics
  • Gene regulation
  • Chromatin
  • Nucleosome positioning
  • Transcription
  • Micro RNA's
  • Algorithm development
  • Biochemistry
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