DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

Transcriptional regulation in response to environmental and developmental cues is mediated by the combinatorial and synergistic action of specific DNA-binding proteins on components of the general transcription machinery and on chromatin modifying activities. This laboratory combines genetic, molecular, and genomic approaches available in yeast and human cells to investigate a variety of issues. These include molecular mechanisms of transcriptional activation, relationship between chromatin structure of DNA and gene expression with particular emphasis epigenetic inheritance, and global transcriptional repression mechanisms mediated by corepressors that are recruited to specific genes. In addition, we are using genomic approaches to analyze transcriptional profiles and transcription factor occupancy during the transition of normal to transformed cells. Lastly, we are part of the ENCODE consortium to analyze genome-wide occupancy of transcription factors and chromatin-modifying activities in human cells.

Publications

• , Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, Kuehn MS, Taylor CM, Neph S, Koch CM, Asthana S, Malhotra A, Adzhubei I, Greenbaum JA, Andrews RM, Flicek P, Boyle PJ, Cao H, Car
  17571346
• Yang A, Zhu Z, Kapranov P, McKeon F, Church GM, Gingeras TR, Struhl K.Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells.Mol Cell 2006 Nov 17;24(4):593-602.
  17188034
• Schwabish MA, Struhl K.Asf1 mediates histone eviction and deposition during elongation by RNA polymerase II.Mol Cell 2006 May 5;22(3):415-22.
  16678113
• Cawley S, Bekiranov S, Ng HH, Kapranov P, Sekinger EA, Kampa D, Piccolboni A, Sementchenko V, Cheng J, Williams AJ, Wheeler R, Wong B, Drenkow J, Yamanaka M, Patel S, Brubaker S, Tammana H, Helt G, Struhl K, Gingeras TR.Unbiased mapping of transcription f
  14980218
• Kadosh D, Struhl K.Targeted recruitment of the Sin3-Rpd3 histone deacetylase complex generates a highly localized domain of repressed chromatin in vivo.Mol Cell Biol 1998 Sep;18(9):5121-7.
  9710596
• Moqtaderi Z, Bai Y, Poon D, Weil PA, Struhl K.TBP-associated factors are not generally required for transcriptional activation in yeast.Nature 1996 Sep 12;383(6596):188-91.
  8774887
• Thakur JK, Arthanari H, Yang F, Pan SJ, Fan X, Breger J, Frueh DP, Gulshan K, Li DK, Mylonakis E, Struhl K, Moye-Rowley WS, Cormack BP, Wagner G, Naar AM.A nuclear receptor-like pathway regulating multidrug resistance in fungi.Nature 2008 Apr 3;452(7187):
  18385733
• Moqtaderi Z, Struhl K.Expanding the repertoire of plasmids for PCR-mediated epitope tagging in yeast.Yeast 2008 Apr;25(4):287-92.
  18338317
• Johnson DS, Li W, Gordon DB, Bhattacharjee A, Curry B, Ghosh J, Brizuela L, Carroll JS, Brown M, Flicek P, Koch CM, Dunham I, Bieda M, Xu X, Farnham PJ, Kapranov P, Nix DA, Gingeras TR, Zhang X, Holster H, Jiang N, Green RD, Song JS, McCuine SA, Anton E,
  18258921
• Ghosh S, Hirsch HA, Sekinger EA, Kapranov P, Struhl K, Gingeras TR.Differential analysis for high density tiling microarray data.BMC Bioinformatics 2007;8:359.
  17892592
• Miotto B, Struhl K.[Histone H4 lysine 16 acetylation: from genome regulation to tumoral progression].Med Sci (Paris) 2007 Aug-Sep;23(8-9):735-40.
  17875292
• Schwabish MA, Struhl K.The Swi/Snf complex is important for histone eviction during transcriptional activation and RNA polymerase II elongation in vivo.Mol Cell Biol 2007 Oct;27(20):6987-95.
  17709398
• Peckham HE, Thurman RE, Fu Y, Stamatoyannopoulos JA, Noble WS, Struhl K, Weng Z.Nucleosome positioning signals in genomic DNA.Genome Res 2007 Aug;17(8):1170-7.
  17620451
• Wade JT, Struhl K, Busby SJ, Grainger DC.Genomic analysis of protein-DNA interactions in bacteria: insights into transcription and chromosome organization.Mol Microbiol 2007 Jul;65(1):21-6.
  17581117
• Reppas NB, Wade JT, Church GM, Struhl K.The transition between transcriptional initiation and elongation in E. coli is highly variable and often rate limiting.Mol Cell 2006 Dec 8;24(5):747-57.
  17157257
• Wade JT, Roa DC, Grainger DC, Hurd D, Busby SJ, Struhl K, Nudler E.Extensive functional overlap between sigma factors in Escherichia coli.Nat Struct Mol Biol 2006 Sep;13(9):806-14.
  16892065
• Proft M, Mas G, de Nadal E, Vendrell A, Noriega N, Struhl K, Posas F.The stress-activated Hog1 kinase is a selective transcriptional elongation factor for genes responding to osmotic stress.Mol Cell 2006 Jul 21;23(2):241-50.
  16857590
• Hall DB, Wade JT, Struhl K.An HMG protein, Hmo1, associates with promoters of many ribosomal protein genes and throughout the rRNA gene locus in Saccharomyces cerevisiae.Mol Cell Biol 2006 May;26(9):3672-9.
  16612005
• Fan X, Chou DM, Struhl K.Activator-specific recruitment of Mediator in vivo.Nat Struct Mol Biol 2006 Feb;13(2):117-20.
  16429153
• Joshi AA, Struhl K.Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation.Mol Cell 2005 Dec 22;20(6):971-8.
  16364921
• Sekinger EA, Moqtaderi Z, Struhl K.Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast.Mol Cell 2005 Jun 10;18(6):735-48.
  15949447
• Katan-Khaykovich Y, Struhl K.Heterochromatin formation involves changes in histone modifications over multiple cell generations.EMBO J 2005 Jun 15;24(12):2138-49.
  15920479
• Mason PB, Struhl K.Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo.Mol Cell 2005 Mar 18;17(6):831-40.
  15780939
• Wade JT, Hall DB, Struhl K.The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes.Nature 2004 Dec 23;432(7020):1054-8.
  15616568
• Schwabish MA, Struhl K.Evidence for eviction and rapid deposition of histones upon transcriptional elongation by RNA polymerase II.Mol Cell Biol 2004 Dec;24(23):10111-7.
  15542822
• Proft M, Struhl K.MAP kinase-mediated stress relief that precedes and regulates the timing of transcriptional induction.Cell 2004 Aug 6;118(3):351-61.
  15294160
• Geisberg JV, Struhl K.Cellular stress alters the transcriptional properties of promoter-bound Mot1-TBP complexes.Mol Cell 2004 May 21;14(4):479-89.
  15149597
• Moqtaderi Z, Struhl K.Genome-wide occupancy profile of the RNA polymerase III machinery in Saccharomyces cerevisiae reveals loci with incomplete transcription complexes.Mol Cell Biol 2004 May;24(10):4118-27.
  15121834
• Mason PB, Struhl K.The FACT complex travels with elongating RNA polymerase II and is important for the fidelity of transcriptional initiation in vivo.Mol Cell Biol 2003 Nov;23(22):8323-33.
  14585989
• Ng HH, Robert F, Young RA, Struhl K.Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity.Mol Cell 2003 Mar;11(3):709-19.
  12667453
• Ng HH, Ciccone DN, Morshead KB, Oettinger MA, Struhl K.Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation.Proc Natl Acad Sci U S A 2003 Feb 18;100(4):1820-5.
  12574507
• Deckert J, Struhl K.Targeted recruitment of Rpd3 histone deacetylase represses transcription by inhibiting recruitment of Swi/Snf, SAGA, and TATA binding protein.Mol Cell Biol 2002 Sep;22(18):6458-70.
  12192044
• Ng HH, Xu RM, Zhang Y, Struhl K.Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79.J Biol Chem 2002 Sep 20;277(38):34655-7.
  12167634
• Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, Zhang Y.Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.Curr Biol 2002 Jun 25;12(12):1052-8.
  12123582
• Proft M, Struhl K.Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress.Mol Cell 2002 Jun;9(6):1307-17.
  12086627
• Ng HH, Feng Q, Wang H, Erdjument-Bromage H, Tempst P, Zhang Y, Struhl K.Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association.Genes Dev 2002 Jun 15;16(12):1518-27.
  12080090
• Mencía M, Moqtaderi Z, Geisberg JV, Kuras L, Struhl K.Activator-specific recruitment of TFIID and regulation of ribosomal protein genes in yeast.Mol Cell 2002 Apr;9(4):823-33.
  11983173
• Strässer K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondón AG, Aguilera A, Struhl K, Reed R, Hurt E.TREX is a conserved complex coupling transcription with messenger RNA export.Nature 2002 May 16;417(6886):304-8.
  11979277
• Ng HH, Robert F, Young RA, Struhl K.Genome-wide location and regulated recruitment of the RSC nucleosome-remodeling complex.Genes Dev 2002 Apr 1;16(7):806-19.
  11937489
• Katan-Khaykovich Y, Struhl K.Dynamics of global histone acetylation and deacetylation in vivo: rapid restoration of normal histone acetylation status upon removal of activators and repressors.Genes Dev 2002 Mar 15;16(6):743-52.
  11914279
• Reid JL, Iyer VR, Brown PO, Struhl K.Coordinate regulation of yeast ribosomal protein genes is associated with targeted recruitment of Esa1 histone acetylase.Mol Cell 2000 Dec;6(6):1297-307.
  11163204
• Dorris DR, Struhl K.Artificial recruitment of TFIID, but not RNA polymerase II holoenzyme, activates transcription in mammalian cells.Mol Cell Biol 2000 Jun;20(12):4350-8.
  10825198
• Kuras L, Kosa P, Mencia M, Struhl K.TAF-Containing and TAF-independent forms of transcriptionally active TBP in vivo.Science 2000 May 19;288(5469):1244-8.
  10818000
• Struhl K.Fundamentally different logic of gene regulation in eukaryotes and prokaryotes.Cell 1999 Jul 9;98(1):1-4.
  10412974
• Kuras L, Struhl K.Binding of TBP to promoters in vivo is stimulated by activators and requires Pol II holoenzyme.Nature 1999 Jun 10;399(6736):609-13.
  10376605
• Moqtaderi Z, Keaveney M, Struhl K.The histone H3-like TAF is broadly required for transcription in yeast.Mol Cell 1998 Nov;2(5):675-82.
  9844639
• Keaveney M, Struhl K.Activator-mediated recruitment of the RNA polymerase II machinery is the predominant mechanism for transcriptional activation in yeast.Mol Cell 1998 May;1(6):917-24.
  9660975
• Kadosh D, Struhl K.Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo.Genes Dev 1998 Mar 15;12(6):797-805.
  9512514
• Struhl K.Histone acetylation and transcriptional regulatory mechanisms.Genes Dev 1998 Mar 1;12(5):599-606.
  9499396
• Kadosh D, Struhl K.Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters.Cell 1997 May 2;89(3):365-71.
  9150136
• De Rubertis F, Kadosh D, Henchoz S, Pauli D, Reuter G, Struhl K, Spierer P.The histone deacetylase RPD3 counteracts genomic silencing in Drosophila and yeast.Nature 1996 Dec 12;384(6609):589-91.
  8955276
• Struhl K.Chromatin structure and RNA polymerase II connection: implications for transcription.Cell 1996 Jan 26;84(2):179-82.
  8565061
• Chatterjee S, Struhl K.Connecting a promoter-bound protein to TBP bypasses the need for a transcriptional activation domain.Nature 1995 Apr 27;374(6525):820-2.
  7723828
• Tzamarias D, Struhl K.Distinct TPR motifs of Cyc8 are involved in recruiting the Cyc8-Tup1 corepressor complex to differentially regulated promoters.Genes Dev 1995 Apr 1;9(7):821-31.
  7705659
• Struhl K.Yeast transcriptional regulatory mechanisms.Annu Rev Genet 1995;29:651-74.
  8825489