Sevinc Ercan

Ph.D., Pennsylvania State University

B.S., Bilkent University, Turkey

Eukaryotic genomes must be condensed to fit inside a small nucleus yet still allow access for gene expression. DNA is packaged hierarchically starting from nucleosomes to chromatin fibers that fold and organize into individual chromosome territories within the nucleus. Packaging at each level regulates transcription. For instance, nucleosomes reduce DNA accessibility to transcription factors and RNA Polymerase. Looping of chromatin fibers mediate regulatory interactions between enhancers and promoters. The link between higher level of chromosome organization and gene expression remains unclear. At the domain-scale, genes across hundreds of kilobases of DNA can be coordinately regulated in clusters – for example the Hox gene cluster and the X chromosome. The goal of our lab is to uncover the molecular mechanisms that specify and regulate large chromosomal domains. The questions that drive our current research are: How are chromosomal domains specified and targeted for gene regulation? What are the transcriptional mechanisms that regulate multiple genes across a domain? What are the functional and evolutionary consequences of domain-scale gene regulation?

To understand the mechanisms of domain-scale gene regulation, we mainly study X chromosome dosage compensation in Caenorhabditis elegans. Dosage compensation is an essential developmental process that equalizes X chromosome transcription between sexes in many animals, including humans. Although strategies differ between species, in the model organisms M. musculus (mouse), D. melanogaster (fly) and C. elegans (worm), multi-subunit dosage compensation complexes (DCC) bind to and regulate X chromosome transcription specifically in one sex. The DCC subunit compositions indicate that the different dosage compensation systems co-opted and targeted distinct sets of gene regulatory mechanisms to the X chromosome. Thus, the diverse strategies of X chromosome dosage compensation provide a unique and experimentally tractable window into the mechanisms that target and regulate transcription across large chromosomal domains.

In C. elegans, the DCC specifically binds to and reduces transcription from both X chromosomes by half in XX hermaphrodites. The core of the DCC is a condensin complex, which belongs to the evolutionarily conserved structural maintenance of chromosomes (SMC) family of complexes. Condensins are essential for chromosome condensation and segregation during cell division, and regulate genome organization and gene expression during interphase. Defects in SMC complexes, including condensins disrupt normal chromosomal functions in a wide range of developmental diseases and cancer. Our research on the C. elegans DCC and S. cerevisiae condensin contributes to the mechanistic understanding of SMC complexes in normal development and in disease.

To read more about our current projects visit: https://sites.google.com/site/ercanlab/research. For a lay reader’s summary visit: https://sites.google.com/site/ercanlab/home/lay-readers-summary.

Molecular and Cellular Biology, BIOL-UA 21

Advanced Cell Biology- The Nucleus, BIOL-GA 1051

Developmental Systems, BIOL-GA 2130

Date of these PubMed search results: March 24 2020
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1. Binding of an X-Specific Condensin Correlates with a Reduction in Active Histone Modifications at Gene Regulatory Elements.
   Genetics (2019 Jul) PMC6614895 free full-text archive
   Street LA, Morao AK, Winterkorn LH, Jiao CY, Albritton SE, Sadic M, Kramer M, Ercan S
2. Condensin action and compaction.
   Curr Genet (2019 Apr) PMC6421088 free full-text archive
   Paul MR, Hochwagen A, Ercan S
3. Condensin Depletion Causes Genome Decompaction Without Altering the Level of Global Gene Expression in Saccharomyces cerevisiae.
   Genetics (2018 Sep) PMC6116964 free full-text archive
   Paul MR, Markowitz TE, Hochwagen A, Ercan S
4. Caenorhabditis elegans Dosage Compensation: Insights into Condensin-Mediated Gene Regulation.
   Trends Genet (2018 Jan) PMC5741500 free full-text archive
   Albritton SE, Ercan S
5. Cooperation between a hierarchical set of recruitment sites targets the X chromosome for dosage compensation.
   Elife (2017 May 30) PMC5451215 free full-text archive
   Albritton SE, Kranz AL, Winterkorn LH, Street LA, Ercan S
6. Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans.
   Genetics (2016 Sep) PMC5012400 free full-text archive
   Kramer M, Rao P, Ercan S
7. Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans.
   PLoS Genet (2015 Dec) PMC4671695 free full-text archive
   Kramer M, Kranz AL, Su A, Winterkorn LH, Albritton SE, Ercan S
8. Mechanisms of x chromosome dosage compensation.
   J Genomics (2015) PMC4303597 free full-text archive
   Ercan S
9. Comparative analysis of metazoan chromatin organization.
   Nature (2014 Aug 28) PMC4227084 free full-text archive
   Ho JW, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, Sohn KA, Minoda A, Tolstorukov MY, Appert A, Parker SC, Gu T, Kundaje A, Riddle NC, Bishop E, Egelhofer TA, Hu SS, Alekseyenko AA, Rechtsteiner A, Asker D, Belsky JA, Bowman SK, Chen QB, Chen RA, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska‑Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Schwartz YB, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE, Dernburg AF, Pirrotta V, Kuroda MI, Noble WS, Tullius TD, Kellis M, MacAlpine DM, Strome S, Elgin SC, Liu XS, Lieb JD, Ahringer J, Karpen GH, Park PJ
10. Sex-biased gene expression and evolution of the x chromosome in nematodes.
    Genetics (2014 Jul) PMC4096367 free full-text archive
    Albritton SE, Kranz AL, Rao P, Kramer M, Dieterich C, Ercan S
11. Modern techniques for the analysis of chromatin and nuclear organization in C. elegans.
    WormBook (2014 Apr 2) PMC4781626 free full-text archive
    Askjaer P, Ercan S, Meister P
12. Regulation of the X chromosomes in Caenorhabditis elegans.
    Cold Spring Harb Perspect Biol (2014 Mar 1) PMC3942922 free full-text archive
    Strome S, Kelly WG, Ercan S, Lieb JD
13. Genome-wide analysis of condensin binding in Caenorhabditis elegans.
    Genome Biol (2013) PMC3983662 free full-text archive
    Kranz AL, Jiao CY, Winterkorn LH, Albritton SE, Kramer M, Ercan S
14. H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation.
    PLoS Genet (2012 Sep) PMC3441679 free full-text archive
    Vielle A, Lang J, Dong Y, Ercan S, Kotwaliwale C, Rechtsteiner A, Appert A, Chen QB, Dose A, Egelhofer T, Kimura H, Stempor P, Dernburg A, Lieb JD, Strome S, Ahringer J
15. An inverse relationship to germline transcription defines centromeric chromatin in C. elegans.
    Nature (2012 Apr 8) PMC3538161 free full-text archive
    Gassmann R, Rechtsteiner A, Yuen KW, Muroyama A, Egelhofer T, Gaydos L, Barron F, Maddox P, Essex A, Monen J, Ercan S, Lieb JD, Oegema K, Strome S, Desai A
16. Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.
    Nat Genet (2011 Oct 23) PMC3576853 free full-text archive
    Deng X, Hiatt JB, Nguyen DK, Ercan S, Sturgill D, Hillier LW, Schlesinger F, Davis CA, Reinke VJ, Gingeras TR, Shendure J, Waterston RH, Oliver B, Lieb JD, Disteche CM
17. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.
    Science (2010 Dec 24) PMC3142569 free full-text archive
    Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, Alves P, Chateigner A, Perry M, Morris M, Auerbach RK, Feng X, Leng J, Vielle A, Niu W, Rhrissorrakrai K, Agarwal A, Alexander RP, Barber G, Brdlik CM, Brennan J, Brouillet JJ, Carr A, Cheung MS, Clawson H, Contrino S, Dannenberg LO, Dernburg AF, Desai A, Dick L, Dose AC, Du J, Egelhofer T, Ercan S, Euskirchen G, Ewing B, Feingold EA, Gassmann R, Good PJ, Green P, Gullier F, Gutwein M, Guyer MS, Habegger L, Han T, Henikoff JG, Henz SR, Hinrichs A, Holster H, Hyman T, Iniguez AL, Janette J, Jensen M, Kato M, Kent WJ, Kephart E, Khivansara V, Khurana E, Kim JK, Kolasinska‑Zwierz P, Lai EC, Latorre I, Leahey A, Lewis S, Lloyd P, Lochovsky L, Lowdon RF, Lubling Y, Lyne R, MacCoss M, Mackowiak SD, Mangone M, McKay S, Mecenas D, Merrihew G, Miller DM 3rd, Muroyama A, Murray JI, Ooi SL, Pham H, Phippen T, Preston EA, Rajewsky N, Ratsch G, Rosenbaum H, Rozowsky J, Rutherford K, Ruzanov P, Sarov M, Sasidharan R, Sboner A, Scheid P, Segal E, Shin H, Shou C, Slack FJ, Slightam C, Smith R, Spencer WC, Stinson EO, Taing S, Takasaki T, Vafeados D, Voronina K, Wang G, Washington NL, Whittle CM, Wu B, Yan KK, Zeller G, Zha Z, Zhong M, Zhou X, Ahringer J, Strome S, Gunsalus KC, Micklem G, Liu XS, Reinke V, Kim SK, Hillier LW, Henikoff S, Piano F, Snyder M, Stein L, Lieb JD, Waterston RH
18. High nucleosome occupancy is encoded at X-linked gene promoters in C. elegans.
    Genome Res (2011 Feb) PMC3032927 free full-text archive
    Ercan S, Lubling Y, Segal E, Lieb JD
19. Broad chromosomal domains of histone modification patterns in C. elegans.
    Genome Res (2011 Feb) PMC3032926 free full-text archive
    Liu T, Rechtsteiner A, Egelhofer TA, Vielle A, Latorre I, Cheung MS, Ercan S, Ikegami K, Jensen M, Kolasinska‑Zwierz P, Rosenbaum H, Shin H, Taing S, Takasaki T, Iniguez AL, Desai A, Dernburg AF, Kimura H, Lieb JD, Ahringer J, Strome S, Liu XS
20. The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny.
    PLoS Genet (2010 Sep 2) PMC2932692 free full-text archive
    Rechtsteiner A, Ercan S, Takasaki T, Phippen TM, Egelhofer TA, Wang W, Kimura H, Lieb JD, Strome S
21. The C. elegans dosage compensation complex propagates dynamically and independently of X chromosome sequence.
    Curr Biol (2009 Nov 17) PMC2783177 free full-text archive
    Ercan S, Dick LL, Lieb JD
22. C. elegans dosage compensation: a window into mechanisms of domain-scale gene regulation.
    Chromosome Res (2009) PMID: 19308702
    Ercan S, Lieb JD
23. The genomic distribution and function of histone variant HTZ-1 during C. elegans embryogenesis.
    PLoS Genet (2008 Sep 12) PMC2522285 free full-text archive
    Whittle CM, McClinic KN, Ercan S, Zhang X, Green RD, Kelly WG, Lieb JD
24. Chromatin proteins do double duty.
    Cell (2008 May 30) PMID: 18510918
    Ercan S, Lieb JD
25. X chromosome repression by localization of the C. elegans dosage compensation machinery to sites of transcription initiation.
    Nat Genet (2007 Mar) PMC2753834 free full-text archive
    Ercan S, Giresi PG, Whittle CM, Zhang X, Green RD, Lieb JD
26. New evidence that DNA encodes its packaging.
    Nat Genet (2006 Oct) PMID: 17006463
    Ercan S, Lieb JD
27. Yeast recombination enhancer is stimulated by transcription activation.
    Mol Cell Biol (2005 Sep) PMC1234320 free full-text archive
    Ercan S, Reese JC, Workman JL, Simpson RT
28. Global chromatin structure of 45,000 base pairs of chromosome III in a- and alpha-cell yeast and during mating-type switching.
    Mol Cell Biol (2004 Nov) PMC525486 free full-text archive
    Ercan S, Simpson RT
29. Global nucleosome distribution and the regulation of transcription in yeast.
    Genome Biol (2004) PMC545588 free full-text archive
    Ercan S, Carrozza MJ, Workman JL