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The Erica Larschan Lab
Dosage Compensation in Drosophila melanogaster

How are genes precisely regulated throughout development to prevent disease? We study Drosophila dosage compensation to understand how chromatin domains form within the nucleus and function to spatially and temporally regulate genes.

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Drosophila dosage compensation targets the male X chromosome.

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The speed of RNA Polymerase may be increased in the presence of the MSL Complex, suggesting a mechanism for upregulation.

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  • Larschan E, Alekseyenko AA, Gortchakov AA, Peng S, Li B, Yang P, Workman JL, Park PJ, Kuroda MI, "MSL complex is attracted to genes marked by H3K36 trimethylation using a sequence-independent mechanism."Molecular cell28.1 (2007 Oct 12): 121-33.

    http://www.ncbi.nlm.nih.gov/pubmed/17936709


  • Alekseyenko AA, Peng S, Larschan E, Gorchakov AA, Lee OK, Kharchenko P, McGrath SD, Wang CI, Mardis ER, Park PJ, Kuroda MI, "A sequence motif within chromatin entry sites directs MSL establishment on the Drosophila X chromosome."Cell134.4 (2008 Aug 22): 599-609.

    http://www.ncbi.nlm.nih.gov/pubmed/18724933


  • Gelbart ME, Larschan E, Peng S, Park PJ, Kuroda MI, "Drosophila MSL complex globally acetylates H4K16 on the male X chromosome for dosage compensation."Nature structural & molecular biology16.8 (2009 Aug): 825-32.

    http://www.ncbi.nlm.nih.gov/pubmed/19648925


  • Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC, Ernst J, Sabo PJ, Larschan E, Gorchakov AA, Gu T, Linder-Basso D, Plachetka A, Shanower G, Tolstorukov MY, Luquette LJ, Xi R, Jung YL, Park RW, Bishop EP, Canfield TK, Sandstrom R, Thurman RE, MacAlpine DM, Stamatoyannopoulos JA, Kellis M, Elgin SC, Kuroda MI, Pirrotta V, Karpen GH, Park PJ, "Comprehensive analysis of the chromatin landscape in Drosophila melanogaster."Nature471.7339 (2011 Mar 24): 480-5.

    http://www.ncbi.nlm.nih.gov/pubmed/21179089


  • Larschan E, Bishop EP, Kharchenko PV, Core LJ, Lis JT, Park PJ, Kuroda MI, "X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila."Nature471.7336 (2011 Mar 3): 115-8.

    http://www.ncbi.nlm.nih.gov/pubmed/21368835


  • Alekseyenko AA, Ho JW, Peng S, Gelbart M, Tolstorukov MY, Plachetka A, Kharchenko PV, Jung YL, Gorchakov AA, Larschan E, Gu T, Minoda A, Riddle NC, Schwartz YB, Elgin SC, Karpen GH, Pirrotta V, Kuroda MI, Park PJ, "Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context."PLoS genetics8.4 (2012): e1002646.

    http://www.ncbi.nlm.nih.gov/pubmed/22570616


  • Larschan E, Soruco MM, Lee OK, Peng S, Bishop E, Chery J, Goebel K, Feng J, Park PJ, Kuroda MI, "Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation."PLoS genetics8.7 (2012): e1002830.

    http://www.ncbi.nlm.nih.gov/pubmed/22844249


  • Bateman JR, Larschan E, D'Souza R, Marshall LS, Dempsey KE, Johnson JE, Mellone BG, Kuroda MI, "A genome-wide screen identifies genes that affect somatic homolog pairing in Drosophila."G3 (Bethesda, Md.)2.7 (2012 Jul): 731-40.

    http://www.ncbi.nlm.nih.gov/pubmed/22870396


  • Soruco MM, Chery J, Bishop EP, Siggers T, Tolstorukov MY, Leydon AR, Sugden AU, Goebel K, Feng J, Xia P, Vedenko A, Bulyk ML, Park PJ, Larschan E, "The CLAMP protein links the MSL complex to the X chromosome during Drosophila dosage compensation."Genes & development27.14 (2013 Jul 15): 1551-6.

    http://www.ncbi.nlm.nih.gov/pubmed/23873939


  • Chery J, Larschan E, "X-marks the spot: X-chromosome identification during dosage compensation."Biochimica et biophysica acta1839.3 (2014 Mar): 234-40.

    http://www.ncbi.nlm.nih.gov/pubmed/24406325


  • Soruco MM, Larschan E, "A new player in X identification: the CLAMP protein is a key factor in Drosophila dosage compensation."Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology22.4 (2014 Dec): 505-15.

    http://www.ncbi.nlm.nih.gov/pubmed/25102930


  • Rieder LE, Larschan EN, "Wisdom from the fly."Trends in genetics : TIG30.11 (2014 Nov): 479-81.

    http://www.ncbi.nlm.nih.gov/pubmed/25161083


  • 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, "Comparative analysis of metazoan chromatin organization."Nature512.7515 (2014 Aug 28): 449-52.

    http://www.ncbi.nlm.nih.gov/pubmed/25164756


  • Mieczkowski J, Cook A, Bowman SK, Mueller B, Alver BH, Kundu S, Deaton AM, Urban JA, Larschan E, Park PJ, Kingston RE, Tolstorukov MY, "MNase titration reveals differences between nucleosome occupancy and chromatin accessibility."Nature communications7. (2016 May 6): 11485.

    http://www.ncbi.nlm.nih.gov/pubmed/27151365


  • Day DS, Zhang B, Stevens SM, Ferrari F, Larschan EN, Park PJ, Pu WT, "Comprehensive analysis of promoter-proximal RNA polymerase II pausing across mammalian cell types."Genome biology17.1 (2016 Jun 3): 120.

    http://www.ncbi.nlm.nih.gov/pubmed/27259512


  • Kuzu G, Kaye EG, Chery J, Siggers T, Yang L, Dobson JR, Boor S, Bliss J, Liu W, Jogl G, Rohs R, Singh ND, Bulyk ML, Tolstorukov MY, Larschan E, "Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation."PLoS genetics12.7 (2016 Jul): e1006120.

    http://www.ncbi.nlm.nih.gov/pubmed/27414415


  • Urban JA, Doherty CA, Jordan WT 3rd, Bliss JE, Feng J, Soruco MM, Rieder LE, Tsiarli MA, Larschan EN, "The essential Drosophila CLAMP protein differentially regulates non-coding roX RNAs in male and females."Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology25.2 (2017 Jun): 101-113.

    http://www.ncbi.nlm.nih.gov/pubmed/27995349


  • Kaye EG, Kurbidaeva A, Wolle D, Aoki T, Schedl P, Larschan E, "Drosophila Dosage Compensation Loci Associate with a Boundary-Forming Insulator Complex."Molecular and cellular biology37.21 (2017 Nov 1): .

    http://www.ncbi.nlm.nih.gov/pubmed/28784719


  • Rieder LE, Koreski KP, Boltz KA, Kuzu G, Urban JA, Bowman SK, Zeidman A, Jordan WT 3rd, Tolstorukov MY, Marzluff WF, Duronio RJ, Larschan EN, "Histone locus regulation by the <i>Drosophila</i> dosage compensation adaptor protein CLAMP."Genes & development31.14 (2017 Jul 15): 1494-1508.

    http://www.ncbi.nlm.nih.gov/pubmed/28838946


  • Urban J, Kuzu G, Bowman S, Scruggs B, Henriques T, Kingston R, Adelman K, Tolstorukov M, Larschan E, "Enhanced chromatin accessibility of the dosage compensated Drosophila male X-chromosome requires the CLAMP zinc finger protein."PloS one12.10 (2017): e0186855.

    http://www.ncbi.nlm.nih.gov/pubmed/29077765


Contact us at the Erica Larschan Lab

185 Meeting St.

Box G-266

Providence, RI

02912


erica_larschan@brown.edu

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