Yahli Lorch

All Publications

• Histone Acetylation Inhibits RSC and Stabilizes the+1 Nucleosome. Molecular cell Lorch, Y., Maier-Davis, B., Kornberg, R. D. 2018; 72 (3): 594

  Abstract

  The+1 nucleosome of yeast genes, within which reside transcription start sites, is characterized by histone acetylation, by the displacement of an H2A-H2B dimer, and by a persistent association with the RSC chromatin-remodeling complex. Here we demonstrate the interrelationship of these characteristics and the conversion of a nucleosome to the+1 state invitro. Contrary to expectation, acetylation performs an inhibitory role, preventing the removal of a nucleosome by RSC. Inhibition is due to both enhanced RSC-histone interaction and diminished histone-chaperone interaction. Acetylation does not prevent all RSC activity, because stably bound RSC removes an H2A-H2B dimer on a timescale of seconds in an irreversible manner.

  View details for PubMedID 30401433

• Chromatin-remodeling for transcription QUARTERLY REVIEWS OF BIOPHYSICS Lorch, Y., Kornberg, R. D. 2017; 50

  Abstract

  The nucleosome serves as a general gene repressor, preventing all initiation of transcription except that which is brought about by specific positive regulatory mechanisms. The positive mechanisms begin with chromatin-remodeling by complexes that slide, disrupt, or otherwise alter the structure and organization of nucleosomes. RSC in yeast and its counterpart PBAF in human cells are the major remodeling complexes for transcription. RSC creates a nucleosome-free region in front of a gene, flanked by strongly positioned +1 and -1 nucleosomes, with the transcription start site typically 10-15 bp inside the border of the +1 nucleosome. RSC also binds stably to nucleosomes harboring regulatory elements and to +1 nucleosomes, perturbing their structures in a manner that partially exposes their DNA sequences. The cryo-electron microscope structure of a RSC-nucleosome complex reveals such a structural perturbation, with the DNA largely unwrapped from the nucleosome and likely interacting with a positively charged surface of RSC. Such unwrapping both exposes the DNA and enables its translocation across the histone octamer of the nucleosome by an ATP-dependent activity of RSC. Genetic studies have revealed additional roles of RSC in DNA repair, chromosome segregation, and other chromosomal DNA transactions. These functions of RSC likely involve the same fundamental activities, DNA unwrapping and DNA translocation.

  View details for DOI 10.1017/S003358351700004X

  View details for Web of Science ID 000396423400001

• Chromatin-remodeling and the initiation of transcription QUARTERLY REVIEWS OF BIOPHYSICS Lorch, Y., Kornberg, R. D. 2015; 48 (4): 465-470

  Abstract

  The nucleosome serves as a general gene repressor by the occlusion of regulatory and promoter DNA sequences. Repression is relieved by the SWI/SNF-RSC family of chromatin-remodeling complexes. Research reviewed here has revealed the essential features of the remodeling process.

  View details for DOI 10.1017/S0033583515000116

  View details for Web of Science ID 000364764300011

  View details for PubMedID 26537406

• Role of DNA sequence in chromatin remodeling and the formation of nucleosome-free regions GENES & DEVELOPMENT Lorch, Y., Maier-Davis, B., Kornberg, R. D. 2014; 28 (22): 2492-2497

  Abstract

  AT-rich DNA is concentrated in the nucleosome-free regions (NFRs) associated with transcription start sites of most genes. We tested the hypothesis that AT-rich DNA engenders NFR formation by virtue of its rigidity and consequent exclusion of nucleosomes. We found that the AT-rich sequences present in many NFRs have little effect on the stability of nucleosomes. Rather, these sequences facilitate the removal of nucleosomes by the RSC chromatin remodeling complex. RSC activity is stimulated by AT-rich sequences in nucleosomes and inhibited by competition with AT-rich DNA. RSC may remove NFR nucleosomes without effect on adjacent ORF nucleosomes. Our findings suggest that many NFRs are formed and maintained by an active mechanism involving the ATP-dependent removal of nucleosomes rather than a passive mechanism due to the intrinsic instability of nucleosomes on AT-rich DNA sequences.

  View details for DOI 10.1101/gad.250704.114

  View details for Web of Science ID 000345269300006

  View details for PubMedCentralID PMC4233242

• Selective removal of promoter nucleosomes by the RSC chromatin-remodeling complex NATURE STRUCTURAL & MOLECULAR BIOLOGY Lorch, Y., Griesenbeck, J., Boeger, H., Maier-Davis, B., Kornberg, R. D. 2011; 18 (8): 881-U34

  Abstract

  Purified chromatin rings, excised from the PHO5 locus of Saccharomyces cerevisiae in transcriptionally repressed and activated states, were remodeled with RSC and ATP. Nucleosomes were translocated, and those originating on the promoter of repressed rings were removed, whereas those originating on the open reading frame (ORF) were retained. Treatment of the repressed rings with histone deacetylase diminished the removal of promoter nucleosomes. These findings point to a principle of promoter chromatin remodeling for transcription, namely that promoter specificity resides primarily in the nucleosomes rather than in the remodeling complex that acts upon them.

  View details for DOI 10.1038/nsmb.2072

  View details for Web of Science ID 000293457200006

  View details for PubMedID 21725295

  View details for PubMedCentralID PMC3150231

• Mechanism of chromatin remodeling PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Lorch, Y., Maier-Davis, B., Kornberg, R. D. 2010; 107 (8): 3458-3462

  Abstract

  Results from biochemical and structural studies of the RSC chromatin-remodeling complex prompt a proposal for the remodeling mechanism: RSC binding to the nucleosome releases the DNA from the histone surface and initiates DNA translocation (through one or a small number of DNA base pairs); ATP binding completes translocation, and ATP hydrolysis resets the system. Binding energy thus plays a central role in the remodeling process. RSC may disrupt histone-DNA contacts by affecting histone octamer conformation and through extensive interaction with the DNA. Bulging of the DNA from the octamer surface is possible, and twisting is unavoidable, but neither is the basis of remodeling.

  View details for DOI 10.1073/pnas.1000398107

  View details for Web of Science ID 000275130900035

  View details for PubMedID 20142505

  View details for PubMedCentralID PMC2817641

• An Rtt109-Independent Role for Vps75 in Transcription-Associated Nucleosome Dynamics MOLECULAR AND CELLULAR BIOLOGY Selth, L. A., Lorch, Y., Ocampo-Hafalla, M. T., Mitter, R., Shales, M., Krogan, N. J., Kornberg, R. D., Svejstrup, J. Q. 2009; 29 (15): 4220-4234

  Abstract

  The histone chaperone Vps75 forms a complex with, and stimulates the activity of, the histone acetyltransferase Rtt109. However, Vps75 can also be isolated on its own and might therefore possess Rtt109-independent functions. Analysis of epistatic miniarray profiles showed that VPS75 genetically interacts with factors involved in transcription regulation whereas RTT109 clusters with genes linked to DNA replication/repair. Additional genetic and biochemical experiments revealed a close relationship between Vps75 and RNA polymerase II. Furthermore, Vps75 is recruited to activated genes in an Rtt109-independent manner, and its genome-wide association with genes correlates with transcription rate. Expression microarray analysis identified a number of genes whose normal expression depends on VPS75. Interestingly, histone H2B dynamics at some of these genes are consistent with a role for Vps75 in histone H2A/H2B eviction/deposition during transcription. Indeed, reconstitution of nucleosome disassembly using the ATP-dependent chromatin remodeler Rsc and Vps75 revealed that these proteins can cooperate to remove H2A/H2B dimers from nucleosomes. These results indicate a role for Vps75 in nucleosome dynamics during transcription, and importantly, this function appears to be largely independent of Rtt109.

  View details for DOI 10.1128/MCB.01882-08

  View details for Web of Science ID 000267939400017

  View details for PubMedID 19470761

  View details for PubMedCentralID PMC2715805

• Structure of a RSC-nucleosome complex and insights into chromatin remodeling NATURE STRUCTURAL & MOLECULAR BIOLOGY Chaban, Y., Ezeokonkwo, C., Chung, W., Zhang, F., Kornberg, R. D., Maier-Davis, B., Lorch, Y., Asturias, F. J. 2008; 15 (12): 1272-1277

  Abstract

  ATP-dependent chromatin-remodeling complexes, such as RSC, can reposition, evict or restructure nucleosomes. A structure of a RSC-nucleosome complex with a nucleosome determined by cryo-EM shows the nucleosome bound in a central RSC cavity. Extensive interaction of RSC with histones and DNA seems to destabilize the nucleosome and lead to an overall ATP-independent rearrangement of its structure. Nucleosomal DNA appears disordered and largely free to bulge out into solution as required for remodeling, but the structure of the RSC-nucleosome complex indicates that RSC is unlikely to displace the octamer from the nucleosome to which it is bound. Consideration of the RSC-nucleosome structure and published biochemical information suggests that ATP-dependent DNA translocation by RSC may result in the eviction of histone octamers from adjacent nucleosomes.

  View details for DOI 10.1038/nsmb.1524

  View details for Web of Science ID 000261383900013

  View details for PubMedID 19029894

  View details for PubMedCentralID PMC2659406

• Chromatin rules NATURE STRUCTURAL & MOLECULAR BIOLOGY Kornberg, R. D., Lorch, Y. 2007; 14 (11): 986-988

  View details for Web of Science ID 000250766200002

• Chromatin remodeling by nucleosome disassembly in vitro PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Lorch, Y., Maier-Davis, B., Kornberg, R. D. 2006; 103 (9): 3090-3093

  Abstract

  The RSC chromatin-remodeling complex completely disassembles a nucleosome in the presence of the histone chaperone Nap1 and ATP. Disassembly occurs in a stepwise manner, with the removal of H2A/H2B dimers, followed by the rest of the histones and the release of naked DNA. RSC and related chromatin-remodeling complexes may be responsible for the removal of promoter nucleosomes during transcriptional activation in vivo.

  View details for DOI 10.1073/pnas.0511050103

  View details for Web of Science ID 000235780700018

  View details for PubMedID 16492771

  View details for PubMedCentralID PMC1413907

• Structural basis of eukaryotic gene transcription 130th Nobel Symposium on Molecular Mechanisms in Biological Processes Boeger, H., Bushnell, D. A., Davis, R., Griesenbeck, J., Lorch, Y., Strattan, J. S., Westover, K. D., Kornberg, R. D. ELSEVIER SCIENCE BV. 2005: 899–903

  Abstract

  An RNA polymerase II promoter has been isolated in transcriptionally activated and repressed states. Topological and nuclease digestion analyses have revealed a dynamic equilibrium between nucleosome removal and reassembly upon transcriptional activation, and have further shown that nucleosomes are removed by eviction of histone octamers rather than by sliding. The promoter, once exposed, assembles with RNA polymerase II, general transcription factors, and Mediator in a approximately 3 MDa transcription initiation complex. X-ray crystallography has revealed the structure of RNA polymerase II, in the act of transcription, at atomic resolution. Extension of this analysis has shown how nucleotides undergo selection, polymerization, and eventual release from the transcribing complex. X-ray and electron crystallography have led to a picture of the entire transcription initiation complex, elucidating the mechanisms of promoter recognition, DNA unwinding, abortive initiation, and promoter escape.

  View details for DOI 10.1016/j.febslet.2004.11.027

  View details for Web of Science ID 000226874300013

  View details for PubMedID 15680971

• Chromatin remodeling by DNA bending, not twisting PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Lorch, Y., Davis, B., Kornberg, R. D. 2005; 102 (5): 1329-1332

  Abstract

  Single-stranded regions (gaps) in nucleosomal DNA interfere with action of the RSC chromatin-remodeling complex, monitored by exposure of restriction endonuclease cutting sites. Single-strand breaks (nicks) in the DNA, by contrast, have no effect. Gaps on one side of the cutting site are inhibitory, but gaps on the other side are not. A gap >100 bp from the cutting site is as effective as a gap <20 bp from the site. These findings suggest a remodeling process involving bending, but not twisting, of the DNA and further point to the propagation of a bent region (loop or bulge) from one end of the nucleosome to the other.

  View details for DOI 10.1073/pnas.0409413102

  View details for Web of Science ID 000226877300016

  View details for PubMedID 15677336

  View details for PubMedCentralID PMC546017

• Isolation and assay of the RSC chromatin-remodeling complex from Saccharomyces cerevisiae CHROMATIN AND CHROMATIN REMODELING ENZYMES, PT C Lorch, Y., Kornberg, R. D. 2004; 377: 316-322

  View details for Web of Science ID 000189412900019

  View details for PubMedID 14979034

• Electron microscopic analysis of the RSC chromatin remodeling complex CHROMATIN AND CHROMATIN REMODELING ENZYMES, PT B Asturias, F. J., Ezeokonkwo, C., Kornberg, R. D., Lorch, Y. 2004; 376: 48-62

  View details for Web of Science ID 000189439600004

  View details for PubMedID 14975298

• Structural analysis of the RSC chromatin-remodeling complex PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Asturias, F. J., Chung, W. H., Kornberg, R. D., Lorch, Y. 2002; 99 (21): 13477-13480

  Abstract

  Electron microscopy of the RSC chromatin-remodeling complex reveals a ring of protein densities around a central cavity. The size and shape of the cavity correspond closely to those of a nucleosome. Results of nuclease protection analysis are consistent with nucleosome binding in the cavity. Such binding could explain the ability of RSC to expose nucleosomal DNA in the presence of ATP without loss of associated histones.

  View details for DOI 10.1073/pnas.162504299

  View details for Web of Science ID 000178635700026

  View details for PubMedID 12368485

  View details for PubMedCentralID PMC129698

• Chromatin and transcription: where do we go from here. Current opinion in genetics & development Kornberg, R. D., Lorch, Y. 2002; 12 (2): 249-251

  View details for PubMedID 11915846

• RSC unravels the nucleosome MOLECULAR CELL Lorch, Y., Zhang, M. C., Kornberg, R. D. 2001; 7 (1): 89-95

  Abstract

  RSC and SWI/SNF chromatin-remodeling complexes were previously reported to generate a stably altered nucleosome. We now describe the formation of hybrids between nucleosomes of different sizes, showing that the stably altered structure is a noncovalent dimer. A basis for dimer formation is suggested by an effect of RSC on the supercoiling of closed, circular arrays of nucleosomes. The effect may be explained by the interaction of RSC with DNA at the ends of the nucleosome, which could lead to the release 60--80 bp or more from the ends. DNA released in this way may be trapped in the stable dimer or lead to alternative fates such as histone octamer transfer to another DNA or sliding along the same DNA molecule.

  View details for Web of Science ID 000166601300009

  View details for PubMedID 11172714

• Mediator-nucleosome interaction MOLECULAR CELL Lorch, Y., Beve, J., Gustafsson, C. M., Myers, L. C., Kornberg, R. D. 2000; 6 (1): 197-201

  Abstract

  Mediator, a multiprotein complex involved in the regulation of RNA polymerase II transcription, binds to nucleosomes and acetylates histones. Three lines of evidence identify the Nut1 subunit of Mediator as responsible for the histone acetyltransferase (HAT) activity. An "in-gel" HAT assay reveals a single band of the appropriate size. Sequence alignment shows significant similarity of Nut1 to the GCN5-related N-acetyltransferase superfamily. Finally, recombinant Nut1 exhibits HAT activity in an in-gel assay.

  View details for Web of Science ID 000088799400020

  View details for PubMedID 10949041

• Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome CELL Kornberg, R. D., Lorch, Y. L. 1999; 98 (3): 285-294

  View details for Web of Science ID 000081950300004

  View details for PubMedID 10458604

• Chromatin-modifying and -remodeling complexes CURRENT OPINION IN GENETICS & DEVELOPMENT Kornberg, R. D., Lorch, Y. 1999; 9 (2): 148-151

  Abstract

  Nucleosomes have long been known to inhibit DNA transactions on chromosomes and a remarkable abundance of multiprotein complexes that either enhance or relieve this inhibition have been described. Most is known about chromatin-remodeling complexes that perturb nucleosome structure.

  View details for Web of Science ID 000079591600004

  View details for PubMedID 10322131

• Histone octamer transfer by a chromatin-remodeling complex CELL Lorch, Y., Zhang, M., Kornberg, R. D. 1999; 96 (3): 389-392

  Abstract

  RSC, an abundant, essential chromatin-remodeling complex related to SWI/SNF complex, catalyzes the transfer of a histone octamer from a nucleosome core particle to naked DNA. The newly formed octamer-DNA complex is identical with a nucleosome in all respects. The reaction requires ATP and involves an activated RSC-nucleosome intermediate. The mechanism may entail formation of a duplex displacement loop on the nucleosome, facilitating the entry of exogeneous DNA and the release of the endogenous molecule.

  View details for Web of Science ID 000078514600011

  View details for PubMedID 10025404

• Activated RSC-nucleosome complex and persistently altered form of the nucleosome CELL Lorch, Y., Cairns, B. R., Zhang, M. C., Kornberg, R. D. 1998; 94 (1): 29-34

  Abstract

  RSC, an abundant, essential chromatin-remodeling complex, related to SWI/SNF complex, binds nucleosomes and naked DNA with comparable affinities, as shown by gel shift analysis. The RSC-nucleosome complex is converted in the presence of ATP to a slower migrating form. This activated complex exhibits greatly increased susceptibility to endo- and exonucleases but retains a full complement of histones. Activation persists in the absence of ATP, and on removal of RSC, the nucleosome is released in an altered form, with a diminished electrophoretic mobility, greater sedimentation rate, and marked instability at elevated ionic strength. The reaction is reversible in the presence of RSC and ATP, with conversion of the altered form back to the nucleosome.

  View details for Web of Science ID 000074790800006

  View details for PubMedID 9674424

• RSC, an essential, abundant chromatin-remodeling complex CELL Cairns, B. R., Lorch, Y., Li, Y., Zhang, M. C., Lacomis, L., ERDJUMENTBROMAGE, H., Tempst, P., Du, J., Laurent, B., Kornberg, R. D. 1996; 87 (7): 1249-1260

  Abstract

  A novel 15-subunit complex with the capacity to remodel the structure of chromatin, termed RSC, has been isolated from S. cerevisiae on the basis of homology to the SWI/SNF complex. At least three RSC subunits are related to SWI/SNF polypeptides: Sth1p, Rsc6p, and Rsc8p are significantly similar to Swi2/Snf2p, Swp73p, and Swi3p, respectively, and were identified by mass spectrometric and sequence analysis of peptide fragments. Like SWI/SNF, RSC exhibits a DNA-dependent ATPase activity stimulated by both free and nucleosomal DNA and a capacity to perturb nucleosome structure. RSC is, however, at least 10-fold more abundant than SWI/SNF complex and is essential for mitotic growth. Contrary to a report for SWII/SNF complex, no association of RSC (nor of SWI/SNF complex) with RNA polymerase II holoenzyme was detected.

  View details for Web of Science ID A1996WA54100013

  View details for PubMedID 8980231

• INTERPLAY BETWEEN CHROMATIN STRUCTURE AND TRANSCRIPTION CURRENT OPINION IN CELL BIOLOGY Kornberg, R. D., Lorch, Y. 1995; 7 (3): 371-375

  Abstract

  Research on the interplay between chromatin and transcription has progressed along three lines during the past year. Evidence has been reported for disruption of nucleosomes by transcriptional regulatory proteins in cell-free systems; displacement of the histone octamer during transcription has been conclusively demonstrated; and insights into transcriptional repression by heterochromatin have been gained from studies of silent mating loci and telomeres in yeast.

  View details for Web of Science ID A1995RB16000011

  View details for PubMedID 7662367

• ISOLATION OF THE YEAST HISTONE OCTAMER PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Lorch, Y., Kornberg, R. D. 1994; 91 (23): 11032-11034

  Abstract

  Procedures for the extraction and purification of the yeast histone octamer are described. Either mechanical disruption, yielding chromatin fragments, or spheroplast formation with subsequent nuclear isolation was employed. A hexahistidine tag was inserted in the N-terminal region of histone H2B, permitting resolution of the histone octamer from high-salt extracts of nuclei or chromatin to near homogeneity. The histone octamer purified in this way was fully active in reconstitution of nucleosomes.

  View details for Web of Science ID A1994PQ93800057

  View details for PubMedID 7972003

  View details for PubMedCentralID PMC45160

• NEAR-ZERO LINKING DIFFERENCE UPON TRANSCRIPTION FACTOR-IID BINDING TO PROMOTER DNA MOLECULAR AND CELLULAR BIOLOGY Lorch, Y., Kornberg, R. D. 1993; 13 (3): 1872-1875

  Abstract

  Binding of yeast transcription factor IID (TFIID) to the adenoviral major late promoter in circular DNA molecules caused a linking number change of less than 0.1. TFIID on its own therefore fails to unwind DNA appreciably, or else it causes both unwinding and compensatory writhing. Highly purified, recombinant yeast TFIID relaxed supercoiled DNA, because of a contaminant of bacterial topoisomerase I. Relaxing activity of topoisomerase I was enhanced by the adenoviral major late promoter, suggesting an instability of the TATA sequence or a destabilizing effect on flanking DNA.

  View details for Web of Science ID A1993KN57900061

  View details for PubMedID 8382777

  View details for PubMedCentralID PMC359500

• INITIATION ON CHROMATIN TEMPLATES IN A YEAST RNA POLYMERASE-II TRANSCRIPTION SYSTEM GENES & DEVELOPMENT Lorch, Y., Lapointe, J. W., Kornberg, R. D. 1992; 6 (12A): 2282-2287

  Abstract

  Templates were prepared with either the TATA box or transcription start sites of the yeast CYC1 promoter in a nucleosome. In both cases, initiation in an unfractionated yeast RNA polymerase II transcription system was abolished by the nucleosome. The inhibition appeared to be relieved by the activator protein Gal4-VP16 binding to a site upstream of the promoter. Inhibition was not relieved, however, in a transcription system reconstituted from purified components, indicating a requirement for additional factors for the effect of Gal4-VP16.

  View details for Web of Science ID A1992KB97700005

  View details for PubMedID 1459452

• CHROMATIN STRUCTURE AND TRANSCRIPTION ANNUAL REVIEW OF CELL BIOLOGY Kornberg, R. D., Lorch, Y. 1992; 8: 563-687

  View details for Web of Science ID A1992JZ40200019

  View details for PubMedID 1335747

• IRRESISTIBLE FORCE MEETS IMMOVABLE OBJECT - TRANSCRIPTION AND THE NUCLEOSOME CELL Kornberg, R. D., Lorch, Y. 1991; 67 (5): 833-836

  View details for Web of Science ID A1991GT75500001

  View details for PubMedID 1959130

• INTERCHANGEABLE RNA-POLYMERASE-I AND POLYMERASE-II ENHANCERS PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Lorch, Y., Lue, N. F., Kornberg, R. D. 1990; 87 (21): 8202-8206

  Abstract

  The RNA polymerase I (pol I) enhancer of Saccharomyces cerevisiae contains at least three elements commonly associated with RNA polymerase II (pol II) enhancers, binding sites for the transcriptional activators general regulatory factor 2 and autonomously replicating sequence-binding factor I, and a thymidine-rich element. When the particular form of the thymidine-rich element found in the pol I enhancer was placed in front of a pol II promoter, transcription was stimulated 43-fold, comparable to the effect of a powerful pol II activator such as Gal4. Conversely, when two copies of a thymidine-rich element from a pol II enhancer were placed upstream of a pol I promoter, transcription was stimulated 38-fold. This functional reciprocity of pol I and II enhancers may reflect similarities in the mechanisms of transcriptional activation. The pol I enhancer also contains an element that appears to be pol I-specific and prevent the activation of pol II.

  View details for Web of Science ID A1990EG22000004

  View details for PubMedID 2236033

• A YEAST PROTEIN THAT INFLUENCES THE CHROMATIN STRUCTURE OF UASG AND FUNCTIONS AS A POWERFUL AUXILIARY GENE ACTIVATOR GENES & DEVELOPMENT Chasman, D. I., Lue, N. F., Buchman, A. R., Lapointe, J. W., Lorch, Y., Kornberg, R. D. 1990; 4 (4): 503-514

  Abstract

  GRF2, an abundant yeast protein of Mr approximately 127,000, binds to the GAL upstream activating sequence (UASG) and creates a nucleosome-free region of approximately 230 bp. Purified GRF2 binds to sequences found in many other UASs, in the 35S rRNA enhancer, at centromeres, and at telomeres. Although GRF2 stimulates transcription only slightly on its own, it combines with a neighboring weak activator to give as much as a 170-fold enhancement. This effect of GRF2 is strongly distance-dependent, declining by 85% when 22 bp is interposed between the GRF2 and neighboring activator sites.

  View details for Web of Science ID A1990DD09700003

  View details for PubMedID 2361590

• PREPARATION OF NUCLEOSOMES AND CHROMATIN METHODS IN ENZYMOLOGY Kornberg, R. D., Lapointe, J. W., Lorch, Y. 1989; 170: 3-14

  View details for Web of Science ID A1989AV25900001

  View details for PubMedID 2770543

• ON THE DISPLACEMENT OF HISTONES FROM DNA BY TRANSCRIPTION CELL Lorch, Y., Lapointe, J. W., Kornberg, R. D. 1988; 55 (5): 743-744

  View details for Web of Science ID A1988R318500002

  View details for PubMedID 3191529

• NUCLEOSOMES INHIBIT THE INITIATION OF TRANSCRIPTION BUT ALLOW CHAIN ELONGATION WITH THE DISPLACEMENT OF HISTONES CELL Lorch, Y., Lapointe, J. W., Kornberg, R. D. 1987; 49 (2): 203-210

  Abstract

  Promoters were assembled in nucleosomes or ligated to nucleosomes and transcribed with SP6 RNA polymerase or with mammalian RNA polymerase II and accessory factors. Neither polymerase would initiate transcription at a promoter in a nucleosome, but once engaged in transcription, both polymerases were capable of reading through a nucleosome. In the course of readthrough transcription, the histones were displaced from the DNA, as shown by the exposure of restriction sites and by a shift of the template to the position of naked DNA in a gel. It may be true, in general, that processive enzymes will traverse regions of DNA organized in nucleosomes and displace histones.

  View details for Web of Science ID A1987H015800009

  View details for PubMedID 3568125

• MONOCLONAL ANTI-I-A ANTIBODY REVERSES CHRONIC PARALYSIS AND DEMYELINATION IN THEILER VIRUS-INFECTED MICE - CRITICAL IMPORTANCE OF TIMING OF TREATMENT JOURNAL OF VIROLOGY Friedmann, A., Frankel, G., Lorch, Y., Steinman, L. 1987; 61 (3): 898-903

  Abstract

  Susceptibility to demyelination caused by the WW isolate of Theiler's murine encephalomyelitis viruses is linked to class II genes of the major histocompatibility complex. SJL/J (H-2s) mice, expressing only I-As class II gene products of the major histocompatibility complex, are highly susceptible to Theiler's murine encephalomyelitis virus infection with the WW virus isolate, with chronic paralysis and severe inflammation and demyelination in the central nervous system. The effect of in vivo administration of anti-I-As monoclonal antibodies on Theiler's murine encephalomyelitis virus infection was observed. SJL/J mice were treated in various protocols pre- or postinfection. Anti-I-As monoclonal antibody reversed chronic paralysis and reduced inflammation and demyelination when given after the establishment of persistent infection. The effect was long lasting, but clinical signs, inflammation, and demyelination recurred 2 months after treatment ceased. Anti-I-As antibodies had no effect on viral titers within the central nervous system. The timing of the administration of monoclonal antibodies was critical. Administration of anti-I-As before the establishment of the persistent infection resulted in fatal encephalitis.

  View details for Web of Science ID A1987G030600035

  View details for PubMedID 3492612

  View details for PubMedCentralID PMC254035