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Workman Lab
Jerry Workman, Ph.D.
Investigator
jlw@stowers-institute.org
Workman Lab Research Website		  
Protein Complexes that Modify Chromatin and Regulate Gene Transcription.

     Eukaryotic chromosomes comprise DNA that is complexed with small basic proteins, histones, and other proteins to generate chromatin, a nucleic acid: protein complex. The tight association of these proteins with DNA provides a level of transcription control and contributes to epigenetic mechanisms of gene regulation. For example, the amino-terminal tail domains of the core histone proteins are sights of numerous post-translational modifications. In addition to potential effects on chromatin structure, these modifications act as binding sites/receptors for protein complexes that activate or repress gene transcription. Thus, histone modification can be used to generate a "code" of signals on the surface of the chromosome fiber, which provides regulatory information above that contained in the DNA sequence. Our laboratory is focused on studying the protein complexes that carry out these histone modifications and those that recognize the resulting signals.

Purification and Analysis of Histone Acetyltransferase Complexes
     Since the discovery of histone acetylation over three decades ago, a strong connection has been shown between the acetylation of histone proteins and transcriptional activity. Over the past several years, a number of the enzymes that carry out these modifications have been identified. We have purified and characterized the native protein HAT (histone acetyltransferase) complexes bearing these enzymes to understand their recruitment to promoter DNA and their function in gene regulation. Thus far we have identified and characterized six such complexes from yeast. These include the 2-MDa SAGA (Spt-Ada-Gcn5-acetyltransferase) complex, the related SLIK (SAGA-like) complex, the 0.8-MDa ADA complex, the 1.3-MDa NuA4 (nucleosome acetyltransferase of histone H4) complex, the 0.4-MDa NuA3 complex, and the 0.4-MDa SAS (something about silencing) complex.

Recruitment of Histone Acetyltransferase Complexes by Transcription Activators to Acetylate Promoter Nucleosomes
     The SAGA complex comprises more than 20 different subunits, which include several different classes of proteins implicated in transcription regulation. SAGA contains Ada proteins, the TATA box–binding protein (TBP) group of Spt gene products, a subset of TBP-associated factors (TAFIIs), and the 400-kDa Tra1 protein. Tra1 is related to the ataxia telangiectasia mutated (ATM) family of phosphatidylinositol 3-kinases and is the yeast homolog of the human TRRAP protein, which plays an essential role in cellular transformation by the c-Myc and E2F oncogenes. Tra1 is also the largest subunit of the NuA4 complex, which also contains a number of gene products implicated in transcriptional regulation. Its catalytic subunit is Esa1 (essential SAS-related acetyltransferase 1).

     Although SAGA primarily acetylates histone H3 and NuA4 histone H4, they share a number of biochemical properties. Our studies have shown that both SAGA and NuA4 interact specifically with the activation domains of promoter-binding transcription activators. When recruited to a promoter through these interactions, either SAGA or NuA4 acetylates promoter-proximal nucleosomes, which results in transcriptional enhancement. Through a series of biochemical and genetic experiments, we have shown that interactions of SAGA and NuA4 with transcription activators occur through the shared Tra1 subunit. Tra1 directs the HAT complexes to promoters via interactions with transcription activators where they lay down a narrow (SAGA) or wide (NuA4) patch of acetylation on histones contained in nucleosomes (repeating histone:DNA complexes) surrounding the promoter. In addition to characterizing the SAGA and NuA4 complexes further, we are also investigating the function of the acetylated patches laid down by these HATs at promoters in chromatin.

Promoter Recruitment and Retention of the SWI/SNF Chromatin Remodeling Complex: Linking Histone Acetylation to Nucleosome Disruption
     The yeast SWI/SNF complex is a 1-Mda-protein complex that is required for the transcription of a subset of yeast genes. Mechanistic studies, by others and us, have demonstrated that SWI/SNF uses the energy of ATP hydrolysis to alter the structure and location of nucleosomes. Through a series of biochemical experiments we have demonstrated that the SWI/SNF complex is also recruited to promoters by direct interactions with the same promoter-binding transcription activators that recruit the SAGA and NuA4 complexes. This suggests that these complexes act in concert during chromatin remodeling, which is consistent with genetic interactions between SAGA and SWI/SNF subunits. We have found that after its recruitment by an activator, the retention of SWI/SNF on the promoter can persist following loss of the activator if adjacent nucleosomes contain acetylated histones. Indeed, prior recruitment of the SAGA or NuA4 HAT complexes to a promoter stabilizes the subsequent binding of SWI/SNF by acetylating promoter-proximal nucleosomes.

Bromodomain Function and Specificity in Anchoring Chromatin Modifying Complexes to Promoters.
     The Swi2/Snf2 subunit of the SWI/SNF complex contains a bromodomain, which has been proposed to be an acetyl-lysine–binding domain. By purifying and analyzing a SWI/SNF complex from which this domain has been deleted, we have found that it is required for SWI/SNF retention on acetylated promoter nucleosomes. Bromodomains are also found in a number of protein complexes involved in transcriptional regulation, including the general transcription factor TFIID and the RSC chromatin-remodeling complex. Thus, histone acetylation has the potential to provide high-affinity interaction sites for bromodomain-containing complexes in chromatin. The SAGA complex itself contains two bromodomains, in the Gcn5 and Spt7 subunits, and is able to stabilize its own binding to promoter nucleosomes by acetylation of histones. This is solely the function of the Gcn5 bromodomain. This specificity of bromodomain function is a consequence of the subunit in which the bromodomain is found. The bromodomains of Spt7, Gcn5 or Swi2 can all serve to anchor SAGA or SWI/SNF onto promoter nucleosomes if placed into the Gcn5 or Swi2 proteins respectively. These studies have illustrated the central role of bromodomains and histone acetylation in the stable binding of chromatin modifying complexes to nucleosomes and communication between them. These interactions are thought to form stable epigenetic marks in chromatin and lead to ordered pathways of chromatin remodeling for transcription.

Histone Acetyltransferase Complexes That Function in Gene Silencing
     While histone acetylation is most often associated with gene activation, it also plays important roles in gene silencing. This is evidenced by the finding of products of the SAS (Something About Silencing) genes in HAT complexes. Others discovered the SAS genes in genetic screens for enhancers of silencing defects at telomeres and mating-type loci in Saccharomyces cerevisiae. The SAS3 gene (a homologue of the human MOZ proto-oncogene) encodes the catalytic subunit of NuA3. SAS3 shares an essential function with GCN5, which results in the death of cells when both genes are mutated. This function cannot be attributed to any of the known Gcn5 containing HAT complexes including SAGA. However, it is clear that the NuA3 complex is involved since deletion of genes encoding other subunits of this complex have similar effects as SAS3 mutations.

     SAS2 encodes an acetyltransferase with significant homology to SAS3 and ESA1. We purified the protein complex containing the Sas2 protein and found that it also contains the protein products of the SAS4 and SAS5 genes. Thus, we simply named this the SAS complex. Surprisingly, the Sas4 component of this complex mediates interactions of the complex with a protein known as Asf1 (anti-silencing function 1). This protein is a histone chaperone/chromatin assembly protein that can interfere with gene silencing when overexpressed in yeast cells. We have found that deletion of ASF1 results in silencing defects similar to the loss of SAS2. We are investigating the functions of the SAS complex and Asf1 in both chromatin assembly and gene silencing.

Selected publications

Suganuma T, Workman JL. Crosstalk among Histone Modifications. Cell. 2008;135:604-607.

Smith KT, Workman JL. Histone deacetylase inhibitors: Anticancer compounds. Int J Biochem Cell Biol. 2008. Abstract

Kwon SH, Workman JL. The Heterochromatin Protein 1 (HP1) Family: Put Away a Bias toward HP1. Mol Cells. 2008;26:217-227. Abstract

Weake VM, Workman JL. Clearing the way for unpaused polymerases. Cell. 2008;134:16-18. Abstract

Suganuma T, Pattenden SG, Workman JL. Diverse functions of WD40 repeat proteins in histone recognition. Genes Dev. 2008;22:1265-1268. Abstract

Weake VM, Workman JL. Histone ubiquitination: triggering gene activity. Mol Cell. 2008;29:653-663. Abstract

Suganuma T, Gutierrez JL, Li B, Florens L, Swanson SK, Washburn MP, Abmayr SM, Workman JL. ATAC is a double histone acetyltransferase complex that stimulates nucleosome sliding. Nat Struct Mol Biol. 2008;15:364-372. Abstract

Weake VM, Lee KK, Guelman S, Lin CH, Seidel C, Abmayr SM, Workman JL. SAGA-mediated H2B deubiquitination controls the development of neuronal connectivity in the Drosophila visual system. Embo J. 2008;27:394-405. Abstract

Li B, Gogol M, Carey M, Pattenden SG, Seidel C, Workman JL. Infrequently transcribed long genes depend on the Set2/Rpd3S pathway for accurate transcription. Genes Dev. 2007;21:1422-1430. Abstract

Li B, Gogol M, Carey M, Lee D, Seidel C, Workman JL. Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin. Science. 2007;316:1050-1054. Abstract

Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell. 2007;128:707-719. Abstract

Gutierrez JL, Chandy M, Carrozza MJ, Workman JL. Activation domains drive nucleosome eviction by SWI/SNF. Embo J. 2007;26:730-740. Abstract

Carey M, Li B, Workman JL. RSC Exploits Histone Acetylation to Abrogate the Nucleosomal Block to RNA Polymerase II Elongation. Mol Cell. 2006;24:481-487. Abstract

Guelman S, Suganuma T, Florens L, Weake V, Swanson SK, Washburn MP, Abmayr SM, Workman JL. The Essential Gene wda Encodes a WD40 Repeat Subunit of Drosophila SAGA Required for Histone H3 Acetylation. Mol Cell Biol. 2006;26:7178-7189. Abstract
 
Shia WJ, Li B, Workman JL. SAS-mediated acetylation of histone H4 Lys 16 is required for H2A.Z incorporation at subtelomeric regions in Saccharomyces cerevisiae. Genes Dev. 2006;20:2507-2512. Abstract

Workman JL. Nucleosome displacement in transcription. Genes Dev. 2006;20:2009-2017. Abstract

Guelman S, Suganuma T, Florens L, Swanson SK, Kiesecker CL, Kusch T, Anderson S, Yates JR, 3rd, Washburn MP, Abmayr SM, Workman JL. Host cell factor and an uncharacterized SANT domain protein are stable components of ATAC, a novel dAda2A/dGcn5-containing histone acetyltransferase complex in Drosophila. Mol Cell Biol. 2006;26:871-882. Abstract

Cai Y, Jin J, Florens L, Swanson SK, Kusch T, Li B, Workman JL, Washburn MP, Conaway RC, Conaway JW. The mammalian YL1 protein is a shared subunit of the TRRAP/TIP60 histone acetyltransferase and SRCAP complexes. J Biol Chem. 2005;280:13665-13670. Abstract

Carrozza MJ, Florens L, Swanson SK, Shia WJ, Anderson S, Yates J, Washburn MP, Workman JL. Stable incorporation of sequence specific repressors Ash1 and Ume6 into the Rpd3L complex. Biochim Biophys Acta. 2005;1731:77-87. Abstract

Carrozza MJ, Li B, Florens L, Suganuma T, Swanson SK, Lee KK, Shia WJ, Anderson S, Yates J, Washburn MP, Workman JL. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell. 2005;123:581-592. Abstract

Ercan S, Reese JC, Workman JL, Simpson RT. Yeast recombination enhancer is stimulated by transcription activation. Mol Cell Biol. 2005;25:7976-7987. Abstract

Jin J, Cai Y, Li B, Conaway RC, Workman JL, Conaway JW, Kusch T. In and out: histone variant exchange in chromatin. Trends Biochem Sci. 2005;30:680-687. Abstract

Jin J, Cai Y, Yao T, Gottschalk AJ, Florens L, Swanson SK, Gutierrez JL, Coleman MK, Workman JL, Mushegian A, Washburn MP, Conaway RC, Conaway JW. A mammalian chromatin remodeling complex with similarities to the yeast INO80 complex. J Biol Chem. 2005;280:41207-41212. Abstract

Lee D, Ezhkova E, Li B, Pattenden SG, Tansey WP, Workman JL. The proteasome regulatory particle alters the SAGA coactivator to enhance its interactions with transcriptional activators. Cell. 2005;123:423-436. Abtract

Lee KK, Florens L, Swanson SK, Washburn MP, Workman JL. The deubiquitylation activity of Ubp8 is dependent upon Sgf11 and its association with the SAGA complex. Mol Cell Biol. 2005;25:1173-1182. Abstract

Li B, Pattenden SG, Lee D, Gutierrez J, Chen J, Seidel C, Gerton J, Workman JL. Preferential occupancy of histone variant H2AZ at inactive promoters influences local histone modifications and chromatin remodeling. Proc Natl Acad Sci U S A. 2005;102:18385-18390. Abstract

Li B, Ruan C, Workman JL. Histones: should I stay or should I go? Genome Biol. 2005;6:306. Abstract

Pattenden SG, Chandy MJ, Gutierrez JL, Workman JL. Chromatin dynamics rule the genome. Genome Biol. 2005;6:355. Abstract

Prochasson P, Florens L, Swanson SK, Washburn MP, Workman JL. The HIR corepressor complex binds to nucleosomes generating a distinct protein/DNA complex resistant to remodeling by SWI/SNF. Genes Dev. 2005;19:2534-2539. Abstract

Ruan C, Workman JL, Simpson RT. The DNA repair protein yKu80 regulates the function of recombination enhancer during yeast mating type switching. Mol Cell Biol. 2005;25:8476-8485. Abstract

Shia WJ, Osada S, Florens L, Swanson SK, Washburn MP, Workman JL. Characterization of the yeast trimeric-SAS acetyltransferase complex. J Biol Chem. 2005;280:11987-11994. Abstract

Ercan S, Carrozza MJ, Workman JL. Global nucleosome distribution and the regulation of transcription in yeast. Genome Biol. 2004;5:243. Abstract

Jeronimo C, Langelier MF, Zeghouf M, Cojocaru M, Bergeron D, Baali D, Forget D, Mnaimneh S, Davierwala AP, Pootoolal J, Chandy M, Canadien V, Beattie BK, Richards DP, Workman JL, Hughes TR, Greenblatt J, Coulombe B. RPAP1, a novel human RNA polymerase II-associated protein affinity purified with recombinant wild-type and mutated polymerase subunits. Mol Cell Biol. 2004;24:7043-7058. Abstract

Kusch T, Florens L, Macdonald WH, Swanson SK, Glaser RL, Yates JR, 3rd, Abmayr SM, Washburn MP, Workman JL. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science. 2004;306:2084-2087. Abstract

Lee KK, Prochasson P, Florens L, Swanson SK, Washburn MP, Workman JL. Proteomic analysis of chromatin-modifying complexes in Saccharomyces cerevisiae identifies novel subunits. Biochem Soc Trans. 2004;32:899-903. Abstract

Robert F, Pokholok DK, Hannett NM, Rinaldi NJ, Chandy M, Rolfe A, Workman JL, Gifford DK, Young RA. Global position and recruitment of HATs and HDACs in the yeast genome. Mol Cell. 2004;16:199-209. Abstract

Vermeulen M, Carrozza MJ, Lasonder E, Workman JL, Logie C, Stunnenberg HG. In vitro targeting reveals intrinsic histone tail specificity of the Sin3/histone deacetylase and N-CoR/SMRT corepressor complexes. Mol Cell Biol. 2004;24:2364-2372. Abstract

Workman JL, Abmayr SM. Histone H3 variants and modifications on transcribed genes. Proc Natl Acad Sci U S A. 2004;101:1429-1430. Abstract

Abmayr SM, Workman JL. Transcription factors prominently in Lasker Award to Roeder. Cell. 2003;115:243-246. Abstract

Carrozza MJ, Hassan AH, Workman JL. Assay of activator recruitment of chromatin-modifying complexes. Methods Enzymol. 2003;371:536-544. Abstract

Carrozza MJ, Kusch T, Workman JL. Repairing nucleosomes during transcription. Nat Struct Biol. 2003;10:879-880. Abstract

Carrozza MJ, Utley RT, Workman JL, Cote J. The diverse functions of histone acetyltransferase complexes. Trends Genet. 2003;19:321-329. Abstract

Kusch T, Guelman S, Abmayr SM, Workman JL. Two Drosophila Ada2 homologues function in different multiprotein complexes. Mol Cell Biol. 2003;23:3305-3319. Abstract

Nourani A, Howe L, Pray-Grant MG, Workman JL, Grant PA, Cote J.  Opposite role of yeast ING family members in p53-dependent transcriptional activation. J Biol Chem. 2003;278:19171-19175. Abstract

Sutton A, Shia WJ, Band D, Kaufman PD, Osada S, Workman JL, Sternglanz R. Sas4 and Sas5 are required for the histone acetyltransferase activity of Sas2 in the SAS complex. J Biol Chem. 2003;273:16887-16892. Abstract

Li B, Howe L, Anderson S, Yates JR III, Workman JL. The Set2 histone methyltransferase functions through the phosphorylated carboxyl-terminal domain of RNA polymerase II. J Biol Chem. 2003;278: 8897-8903. Abstract

Carrozza MJ, Sil AK, Hopper JE, Workman JL. Gal80 confers specificity on HAT complex interactions with activators. J Biol Chem. 2002;277:24648-24652. Abstract

 Hassan AH, Neely KE, Prochasson P, Chandy M, Workman JL.  Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell. 2002;111:369-379. Abstract

Howe L, Kusch T, Muster N, Chaterji R, Yates JR, Workman JL. Yng1p modulates the activity of Sas3p as a component of the yeast NuA3 histone acetyltransferase complex. Mol Cell Biol. 2002;22:5047-5054. Abstract

Neely KE, Hassan AH, Brown CE, Howe L, Workman JL. Transcription activator interactions with multiple SWI/SNF subunits. Mol Cell Biol. 2002;22:1615-1625. Abstract

Pray-Grant MG, Kennedy EL, Schieltz D, Cook R, Workman JL, Yates JR III, Grant PA.  The novel SLIK histone acetyltransferase complex functions in the retrograde response pathway. Mol Cell Biol. 2002;24:;8774-8786. Abstract

Brown CE, Howe L, Sousa K, Alley SC, Tan S, Workman JL. Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit. Science. 2001;292:2333-2337. Abstract

Hassan AH, Neely KE, Workman JL.  Histone acetyltransferase complexes stabilize SWI/SNF binding to promoter nucleosomes. Cell. 2001;104:817-827. Abstract

Howe L, Austin D, Grant P, John S, Cook RG, Workman JL, Pillus L.  Histone H3 specific HATs are essential for cell cycle progression. Genes Dev. 2001;15:3144-3154.
Abstract

Osada S, Sutton A, Muster N, Brown CE, Yates JR, Sternglanz R, Workman JL.  The yeast SAS (something about silencing) protein complex contains a MYST-type acetyltransferase and functions with chromatin assembly factor ASF1. Genes Dev. 2001;15:3155-3168.  Abstract

John S, Howe L, Travov ST, Grant PA, Sternglanz R, Workman JL.  The something about silencing protein, SAS3, is the catalytic subunit of the NuA3 complex, a TAF30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)/FACT complex. Genes Dev. 2000;14:1196-1208. Abstract

Lechner T, Grant PA, Eberharter A, Vannier D, Yu Y, Brosch G, Stillman DJ, Shore D,  Workman JL.  Sds3 (Suppressor of defective silencing 3) is an integral component of the yeast Sin3 / Rpd3 histone deacetylase complex and is required for histone deacetylase activity. J Biol Chem. 2000;275:40961-40966. Abstract

Vignali M, Steger D, Neely K, Workman JL.  Distribution of acetylated histones resulting from Gal4-VP16 recruitment of SAGA and NuA4 complexes. EMBO J. 2000;19:2629-2640. Abstract

Wallberg AE, Neeley KE, Hassan AH, Gustafsson J-A, Workman JL, Wright APH. Recruitment of the SWI-SNF chromatin remodeling complex as a mechanism of gene activation by the glucocorticoid receptor tau1 activation domain. Mol Cell Biol. 2000;20:2004-2013.  Abstract

Allard S, Utley RT, Savard J, Clarke A, Grant P, Brandl CJ, Pillus L, Workman JL, Côté J.  NuA4, an essential transcription adaptor/histone H4 acetyltransferase complex containing Esa1p and the ATM-related cofactor Tra1p. EMBO J. 1999;18:5108-5119. Abstract

Bazett-Jones DP, Côté J, Landel CC, Peterson CL, Workman JL. SWI/SNF complex creates loop domains in DNA and polynucleosome arrays and can disrupt DNA: histone contacts within these domains. Mol Cell Biol. 1999;19:1470-1478. Abstract

Eberharter A, Sterner DE, Schieltz D, Hassan AH, Yates JR 3rd, Berger SL, Workman JL. The ADA complex is a distinct histone acetyltransferase complex in yeast. Mol Cell Biol. 1999;19:6621-6631. Abstract

Grant PA, Eberharter A, John S, Cook RG, Turner BM, Workman JL.  Expanded lysine acetylation specificity of Gcn5 in native complexes. J Biol Chem. 1999;274:5895-5900. Abstract

Ikeda K, Steger DJ, Eberharter A, Workman JL.  Activation domain specific and general transcription stimulation by native histone acetyltransferase complexes. Mol Cell Biol. 1999;19:855-863. Abstract

Massari MB, Grant PA, Pray-Grant MG, Berger SL, Workman JL, Murre C.  A conserved motif present in a class of helix-loop-helix proteins activates transcriptions  by direct recruitment of the SAGA complex. Mol Cell. 1999;4:63-73. Abstract

Neely KE, Hassan AH, Wallberg AE, Steger DJ, Cairns BR, Wright APH, Workman JL. Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays. Mol Cell. 1999;4:649-655. Abstract

Ohba R, Steger DJ, Brownell JE, Mizzen CA, Cook RG, Côté J, Workman JL, Allis CD.  A novel H2A/H4 nucleosomal histone acetyltransferase in Tetrahymena thermophila. Mol Cell Biol. 1999;19:2061-2068. Abstract

Sterner DE, Grant PA, Roberts SM, Duggan LJ, Belotserkovskaya R, Pacella LA, Winston F, Workman JL, Berger SL.  Functional organization of the yeast SAGA complex: distinct components involved in structural integrity, nucleosome acetylation, and TBP binding. Mol Cell Biol. 1999;19:86-98. Abstract

Wallberg AE, Neely KE, Gustafsson J-Å, Workman JL, Wright AP, Grant PA.  HAT complexes can mediate transcriptional activation by the major glucocorticoid receptor activation domain. Mol Cell Biol. 1999;19:5952-5959. Abstract
 
Whitehouse I, Flaus A, Cairns BR, White MF, Workman JL, Owen-Hughes T. Catalytic nucleosome mobilisation mediated by the SWI/SNF complex. Nature. 1999;400:784-787. Abstract

Côté J, Peterson CL, Workman JL. Perturbation of nucleosome structure by the SWI/SNF complex persists following its detachment, enhancing subsequent transcription factor binding. Proc Natl Acad Sci USA. 1998;9:4947-4952. Abstract

Grant PA, Schieltz D, Pray-Grant MG, Yates JR III, Workman JL.  The ATM-related cofactor Tra1 is a component of the purified SAGA complex. Mol Cell. 1998;2:863-867. Abstract

Grant PA, Schieltz D, Pray-Grant MG, Steger DJ, Reese JC, Yates III JR, Workman JL. A subset of TBP-associated factors, TAFIIs, are integral components of the SAGA complex that are required for nucleosome acetylation and transcription stimulation. Cell. 1998;94:45-53. Abstract

Mutskov V, Gerber D, Angelov D, Ausio J, Workman JL, Dimitrov S.  Persistent interactions of the core histone tails with nucleosomal DNA following acetylattion and transcription factor binding. Mol Cell Biol. 1998;18:6298-6304. Abstract

Steger DJ, Eberharter A, John S, Grant PA, Workman JL. Purified histone acetyltransferase complexes stimulate HIV-1 transcription from preassembled nucleosomal arrays. Proc Natl Acad Sci USA. 1998;95: 2924-12929. Abstract

Utley RT, Ikeda K, Grant PA, Côté J, Steger DJ, Eberharter A, John S, Workman JL. Transcriptional activators target histone acetyltransferase complexes to nucleosomes. Nature. 1998;394:498-502. Abstract

Grant PA, Duggan L, Côté J, Roberts SM, Brownell JE, Candau R, Ohba R, Owen-Hughes T, Allis CD, Winston F, Berger SL, Workman JL. Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an ADA complex and the SAGA (Spt/Ada) complex. Genes Dev. 1997;11:1640-1650. Abstract

Juan L-J, Utley RT, Vignali M, Bohm L, Workman JL.  H1-mediated  repression of transcription factor binding to a stably positioned nucleosome. J Biol Chem. 1997;272:3635-3640. Abstract

Steger DJ, Workman JL. Stable co-occupancy of transcription factors and histones at the HIV-1 enhancer. EMBO J. 1997;16:2463-2472. Abstract

Utley RT, Côté J, Owen-Hughes T, Workman JL.  SWI/SNF stimulates the formation of disparate activator-nucleosome complexes but is partially redundant with cooperative binding. J Biol Chem. 1997;272:12642-12649. Abstract

Owen-Hughes TA, Utley RT, Côté J, Peterson CL, Workman JL.  Persistent site specific remodeling of a nucleosome array by transient action of the SWI/SNF complex. Science. 1996;273:513-516. Abstract

Owen-Hughes TA, Workman JL. Remodeling the chromatin structure of a
nucleosome array by transcription factor-targeted trans-displacement of histones. EMBO J. 1996;15:4702-4717. Abstract

Vettese-Dadey M, Grant PA, Hebbes TR, Crane-Robinson C, Allis CD, Workman JL.  Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro. EMBO J. 1996;15:2508-2518. Abstract

Wang W, Côté J, Xue Y, Zhou S, Khavari PA, Biggar SR, Muchardt C, Kalpana GV, Goff SP, Yaniv M, Workman JL, Crabtree GR.  Purification and biochemical heterogeneity of the mammalian SWI/SNF complex. EMBO J. 1996;15:5370-5382. Abstract

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