Chromatin Remodeling and the Control of Gene Expression (1997)

Biochemical and genetic findings accumulated over the past decade have established that the condensation of eukaryotic DNA in chromatin functions not only to constrain the genome within the boundaries of the cell nucleus but also to suppress gene activity in a general manner. This genetic repression extends from the level of the nucleosome, the primary unit of chromatin organization, where coiling of DNA on the surface of the nucleosome core particle impedes access to the transcriptional apparatus, to the higher order folding of nucleosome arrays and the organization of silent regions of chromatin (for reviews see Refs. 1van Holde K. Zlatanova J. Arents G. Moudrianakis E. Elgin S.C.R. Chromatin Structure and Gene Expression. Oxford University Press, Oxford, UK1995: 1-26Google Scholar, 2Ramakrishnan V. Annu. Rev. Biophys. Biomol. Struct. 1997; 26: 83-112Crossref PubMed Scopus (132) Google Scholar, 3Pruss D. Hayes J.J. Wolffe A.P. Bioessays. 1995; 17: 161-170Crossref PubMed Google Scholar, 4Grunstein M. Annu. Rev. Cell Biol. 1990; 6: 643-678Crossref PubMed Google Scholar, 5Kornberg R.D. Lorch Y. Annu. Rev. Cell Biol. 1992; 8: 563-589Crossref PubMed Google Scholar, 6Fletcher T.M. Hansen J.C. Crit. Rev. Eukaryotic Gene Expression. 1996; 6: 149-188Crossref PubMed Google Scholar and 105Koshland D. Strunnikov A. Annu. Rev. Cell Biol. 1996; 12: 305-333Crossref Scopus (283) Google Scholar). Chromatin structure is inextricably linked to transcriptional regulation, and recent studies show how chromatin is perturbed so as to facilitate transcription (for reviews see Refs. 7Adams C.C. Workman J.L. Cell. 1993; 72: 305-308Abstract Full Text PDF PubMed Scopus (134) Google Scholar, 8Paranjape S.M. Kamakaka R.T. Kadonaga J.T. Annu. Rev. Biochem. 1994; 63: 265-297Crossref PubMed Google Scholar, 9Kornberg R.D. Lorch Y. Curr. Opin. Cell Biol. 1995; 7: 371-375Crossref PubMed Scopus (95) Google Scholar, 10Felsenfeld G. Cell. 1996; 86: 13-19Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar, 11Brownell J.E. Allis C.D. Curr. Opin. Genet. Dev. 1996; 6: 176-184Crossref PubMed Scopus (438) Google Scholar, 12Krude T. Elgin S.C.R. Curr. Biol. 1996; 6: 511-515Abstract Full Text Full Text PDF PubMed Google Scholar). Here, we review the substantial advances in the identification of histone acetyltransferases and histone deacetylases, whose opposing activities establish the steady-state level of histone acetylation, and progress in studies of multicomponent systems that require energy for the process of nucleosome disruption.Histone AcetylationSince the early discovery of histone acetylation by Allfrey and colleagues (13Allfrey V.G. Faulkner R. Mirsky A.E. Proc. Natl. Acad. Sci. U. S. A. 1964; 51: 786-794Crossref PubMed Google Scholar), this post-translation modification has been correlated with the processes of transcription and chromatin assembly. Acetylation occurs at specific lysines in the flexible N-terminal histone tails that protrude from the nucleosome surface (11Brownell J.E. Allis C.D. Curr. Opin. Genet. Dev. 1996; 6: 176-184Crossref PubMed Scopus (438) Google Scholar, 14Turner B.M. O'Neil L.P. Semin. Cell Biol. 1995; 6: 229-236Crossref PubMed Google Scholar). Hyperacetylation of histones is associated with transcriptional activity or the potential for activity, whereas histone hypoacetylation is correlated with transcriptionally silent chromatin and heterochromatin. Histone acetylation is also associated with the active deposition and maturation of newly assembled nucleosomes during DNA replication (for reviews see Refs. 14Turner B.M. O'Neil L.P. Semin. Cell Biol. 1995; 6: 229-236Crossref PubMed Google Scholar and 15Loidl P. Chromosoma. 1994; 103: 441-449Crossref PubMed Google Scholar). Acetylation reduces the net positive charge of the histones and weakens interactions with DNA (16Hong L. Schroth G.P. Matthews H.R. Yau P. Bradbury E.M. J. Biol. Chem. 1993; 268: 305-314Abstract Full Text PDF PubMed Google Scholar), inhibits the higher order folding of nucleosome arrays (17Hansen J.C. Wolffe A.P. Biochemistry. 1992; 31: 7977-7988Crossref PubMed Google Scholar, 18Garcia-Ramirez M. Rocchini C. Ausio J. J. Biol. Chem. 1995; 270: 17923-17928Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar), and disrupts specific interactions with nonhistone regulators, as shown for the yeast silencer and repressor proteins Sir3 and Sir4 (19Thompson J.S. Ling X. Grunstein M. Nature. 1994; 369: 245-247Crossref PubMed Scopus (202) Google Scholar, 20Hecht A. Laroche T. Strahl-Bosinger S. Gasser S.M. Grunstein M. Cell. 1995; 80: 583-592Abstract Full Text PDF PubMed Scopus (674) Google Scholar) and Tup-1 (21Edmondson Dev. 1996; PubMed Google Histone and a of and genetic of the of histone histone on the histone substantial with yeast as a transcriptional J.E. J. T. R. Allis C.D. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). of the is for in a genetic histone modification and transcriptional R. Allis C.D. J. 1997; PubMed Scopus Google Scholar). a has been this is to R. L. Cell. Biol. 1996; PubMed Scopus Google Scholar, L. C. C. R. J. Allis C.D. Cell. Biol. 1997; 17: PubMed Google Scholar). yeast histone at and histone at lysines and J.E. Allis C.D. Nature. 1996; PubMed Scopus Google Scholar). the that in the activity on and studies at and that a with R. Allis C.D. J. 1997; PubMed Scopus Google J. L. J. 1994; PubMed Scopus Google Scholar, J. L. Cell. Biol. 1995; PubMed Google Scholar, T. G. Genet. 1995; PubMed Scopus Google Scholar). of to the of the transcriptional and in a by of J. L. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google R. L. P. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google and of or histone acetyltransferases have in the past is a histone on the of to and yeast J. Y. Nature. 1996; PubMed Scopus Google Scholar), with the transcriptional has activity for histones and but is also to histone is a histone with in to the acetyltransferases V. V. Y. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T. Nature. 1996; PubMed Scopus Google Scholar). is in that core histones in or in the acetylation on histone occurs at lysines and the that to acetylation in J. Y. Nature. 1996; PubMed Scopus Google Scholar). and to with transcription by and and also for the (for a review see R. T. Nature. 1996; PubMed Scopus Google Scholar). histones of in to yeast and and proteins a of by a of that a and a to and acetyltransferases C. J. A. L. Genet. 1996; PubMed Scopus Google Scholar, J. R. C. D. S. A.E. Genet. 1996; PubMed Scopus Google Scholar, J. T. D. G. 1996; PubMed Scopus Google Scholar, A. D. A. J. J. 1997; PubMed Scopus Google Scholar). or of proteins in transcriptional and have not been in a of a of with that the acetylation of histones or proteins J. R. C. D. S. A.E. Genet. 1996; PubMed Scopus Google the general transcription of and the associated has been to a the or in the has a activity for of and a activity R. S. R. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T. J.E. T. Workman J.L. T. Y. C.D. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). histone over and has or activity on histones T. J.E. T. Workman J.L. T. Y. C.D. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). of for activity to the and to of activity in that nucleosomes over core the of the activity to for nucleosome of and a histone that as a histone as a for DNA with the core histones A. T. X. Y. R. Nature. 1996; PubMed Scopus Google Scholar, Y. S. M. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, X. T. A. R. Y. Nature. 1996; PubMed Scopus Google with the identification of studies of histone in have also with the a in the and of a J. 1996; PubMed Scopus Google Scholar) of a Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar), and a associated of the to yeast to for repression and of a of M. R. Cell. Biol. PubMed Google Scholar). of in of of the histone as and Grunstein M. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, R. S. Grunstein M. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google from the of the of the and and to of histones and in the of as repression of R. S. Grunstein M. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar). of a of of that of as a histone to gene D. S. D. G. K. P. Nature. 1996; PubMed Scopus Google Scholar). findings to the acetylation of histone at is for transcriptional in yeast M. Allis C.D. B.M. Cell. Biol. 1996; PubMed Google Scholar) and is also associated with in B.M. J. Cell. 1992; Full Text PDF PubMed Google Scholar), net in with the of histone in transcriptional repression is the of the DNA in cell and with and with a transcriptional linked to yeast Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, C.D. E. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). studies also associated with and histone in cell Y. R. P. D. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). a transcription that as a repressor to histone C. Y. D. E. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar), and and for with and histone L. R. J. L. D. Nature. 1997; PubMed Google Scholar, T. T.M. M. 1997; PubMed Google Scholar, L. D. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). of by the yeast also of a and D. K. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). This of for a of repression by the of histone to the of so of chromatin structure a of that for is the of histones during the histones or from and how a structure interactions DNA S. M. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google nucleosomes that or to the structure of DNA have for in chromatin by proteins as and Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar) and by the L. A. D. M. Cell. 1997; Full Text Full Text PDF PubMed Google chromatin for a gene and at of the the of regulators, of the or activities to specific or the chromatin of for by is the of the modification a nucleosome and how is the modification the activities of the histone acetyltransferases and histone with the of nucleosome on higher order chromatin or is by higher order chromatin to and not only for the of gene but also for of Biochemical and genetic findings accumulated over the past decade have established that the condensation of eukaryotic DNA in chromatin functions not only to constrain the genome within the boundaries of the cell nucleus but also to suppress gene activity in a general manner. This genetic repression extends from the level of the nucleosome, the primary unit of chromatin organization, where coiling of DNA on the surface of the nucleosome core particle impedes access to the transcriptional apparatus, to the higher order folding of nucleosome arrays and the organization of silent regions of chromatin (for reviews see Refs. 1van Holde K. Zlatanova J. Arents G. Moudrianakis E. Elgin S.C.R. Chromatin Structure and Gene Expression. Oxford University Press, Oxford, UK1995: 1-26Google Scholar, 2Ramakrishnan V. Annu. Rev. Biophys. Biomol. Struct. 1997; 26: 83-112Crossref PubMed Scopus (132) Google Scholar, 3Pruss D. Hayes J.J. Wolffe A.P. Bioessays. 1995; 17: 161-170Crossref PubMed Google Scholar, 4Grunstein M. Annu. Rev. Cell Biol. 1990; 6: 643-678Crossref PubMed Google Scholar, 5Kornberg R.D. Lorch Y. Annu. Rev. Cell Biol. 1992; 8: 563-589Crossref PubMed Google Scholar, 6Fletcher T.M. Hansen J.C. Crit. Rev. Eukaryotic Gene Expression. 1996; 6: 149-188Crossref PubMed Google Scholar and 105Koshland D. Strunnikov A. Annu. Rev. Cell Biol. 1996; 12: 305-333Crossref Scopus (283) Google Scholar). Chromatin structure is inextricably linked to transcriptional regulation, and recent studies show how chromatin is perturbed so as to facilitate transcription (for reviews see Refs. 7Adams C.C. Workman J.L. Cell. 1993; 72: 305-308Abstract Full Text PDF PubMed Scopus (134) Google Scholar, 8Paranjape S.M. Kamakaka R.T. Kadonaga J.T. Annu. Rev. Biochem. 1994; 63: 265-297Crossref PubMed Google Scholar, 9Kornberg R.D. Lorch Y. Curr. Opin. Cell Biol. 1995; 7: 371-375Crossref PubMed Scopus (95) Google Scholar, 10Felsenfeld G. Cell. 1996; 86: 13-19Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar, 11Brownell J.E. Allis C.D. Curr. Opin. Genet. Dev. 1996; 6: 176-184Crossref PubMed Scopus (438) Google Scholar, 12Krude T. Elgin S.C.R. Curr. Biol. 1996; 6: 511-515Abstract Full Text Full Text PDF PubMed Google Scholar). Here, we review the substantial advances in the identification of histone acetyltransferases and histone deacetylases, whose opposing activities establish the steady-state level of histone acetylation, and progress in studies of multicomponent systems that require energy for the process of nucleosome Histone AcetylationSince the early discovery of histone acetylation by Allfrey and colleagues (13Allfrey V.G. Faulkner R. Mirsky A.E. Proc. Natl. Acad. Sci. U. S. A. 1964; 51: 786-794Crossref PubMed Google Scholar), this post-translation modification has been correlated with the processes of transcription and chromatin assembly. Acetylation occurs at specific lysines in the flexible N-terminal histone tails that protrude from the nucleosome surface (11Brownell J.E. Allis C.D. Curr. Opin. Genet. Dev. 1996; 6: 176-184Crossref PubMed Scopus (438) Google Scholar, 14Turner B.M. O'Neil L.P. Semin. Cell Biol. 1995; 6: 229-236Crossref PubMed Google Scholar). Hyperacetylation of histones is associated with transcriptional activity or the potential for activity, whereas histone hypoacetylation is correlated with transcriptionally silent chromatin and heterochromatin. Histone acetylation is also associated with the active deposition and maturation of newly assembled nucleosomes during DNA replication (for reviews see Refs. 14Turner B.M. O'Neil L.P. Semin. Cell Biol. 1995; 6: 229-236Crossref PubMed Google Scholar and 15Loidl P. Chromosoma. 1994; 103: 441-449Crossref PubMed Google Scholar). Acetylation reduces the net positive charge of the histones and weakens interactions with DNA (16Hong L. Schroth G.P. Matthews H.R. Yau P. Bradbury E.M. J. Biol. Chem. 1993; 268: 305-314Abstract Full Text PDF PubMed Google Scholar), inhibits the higher order folding of nucleosome arrays (17Hansen J.C. Wolffe A.P. Biochemistry. 1992; 31: 7977-7988Crossref PubMed Google Scholar, 18Garcia-Ramirez M. Rocchini C. Ausio J. J. Biol. Chem. 1995; 270: 17923-17928Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar), and disrupts specific interactions with nonhistone regulators, as shown for the yeast silencer and repressor proteins Sir3 and Sir4 (19Thompson J.S. Ling X. Grunstein M. Nature. 1994; 369: 245-247Crossref PubMed Scopus (202) Google Scholar, 20Hecht A. Laroche T. Strahl-Bosinger S. Gasser S.M. Grunstein M. Cell. 1995; 80: 583-592Abstract Full Text PDF PubMed Scopus (674) Google Scholar) and Tup-1 (21Edmondson Dev. 1996; PubMed Google Scholar). the early discovery of histone acetylation by Allfrey and colleagues (13Allfrey V.G. Faulkner R. Mirsky A.E. Proc. Natl. Acad. Sci. U. S. A. 1964; 51: 786-794Crossref PubMed Google Scholar), this post-translation modification has been correlated with the processes of transcription and chromatin assembly. Acetylation occurs at specific lysines in the flexible N-terminal histone tails that protrude from the nucleosome surface (11Brownell J.E. Allis C.D. Curr. Opin. Genet. Dev. 1996; 6: 176-184Crossref PubMed Scopus (438) Google Scholar, 14Turner B.M. O'Neil L.P. Semin. Cell Biol. 1995; 6: 229-236Crossref PubMed Google Scholar). Hyperacetylation of histones is associated with transcriptional activity or the potential for activity, whereas histone hypoacetylation is correlated with transcriptionally silent chromatin and heterochromatin. Histone acetylation is also associated with the active deposition and maturation of newly assembled nucleosomes during DNA replication (for reviews see Refs. 14Turner B.M. O'Neil L.P. Semin. Cell Biol. 1995; 6: 229-236Crossref PubMed Google Scholar and 15Loidl P. Chromosoma. 1994; 103: 441-449Crossref PubMed Google Scholar). Acetylation reduces the net positive charge of the histones and weakens interactions with DNA (16Hong L. Schroth G.P. Matthews H.R. Yau P. Bradbury E.M. J. Biol. Chem. 1993; 268: 305-314Abstract Full Text PDF PubMed Google Scholar), inhibits the higher order folding of nucleosome arrays (17Hansen J.C. Wolffe A.P. Biochemistry. 1992; 31: 7977-7988Crossref PubMed Google Scholar, 18Garcia-Ramirez M. Rocchini C. Ausio J. J. Biol. Chem. 1995; 270: 17923-17928Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar), and disrupts specific interactions with nonhistone regulators, as shown for the yeast silencer and repressor proteins Sir3 and Sir4 (19Thompson J.S. Ling X. Grunstein M. Nature. 1994; 369: 245-247Crossref PubMed Scopus (202) Google Scholar, 20Hecht A. Laroche T. Strahl-Bosinger S. Gasser S.M. Grunstein M. Cell. 1995; 80: 583-592Abstract Full Text PDF PubMed Scopus (674) Google Scholar) and Tup-1 (21Edmondson Dev. 1996; PubMed Google Scholar). Histone and a of and genetic of the of histone histone on the histone substantial with yeast as a transcriptional J.E. J. T. R. Allis C.D. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). of the is for in a genetic histone modification and transcriptional R. Allis C.D. J. 1997; PubMed Scopus Google Scholar). a has been this is to R. L. Cell. Biol. 1996; PubMed Scopus Google Scholar, L. C. C. R. J. Allis C.D. Cell. Biol. 1997; 17: PubMed Google Scholar). yeast histone at and histone at lysines and J.E. Allis C.D. Nature. 1996; PubMed Scopus Google Scholar). the that in the activity on and studies at and that a with R. Allis C.D. J. 1997; PubMed Scopus Google J. L. J. 1994; PubMed Scopus Google Scholar, J. L. Cell. Biol. 1995; PubMed Google Scholar, T. G. Genet. 1995; PubMed Scopus Google Scholar). of to the of the transcriptional and in a by of J. L. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google R. L. P. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). a of and genetic of the of histone histone on the histone substantial with yeast as a transcriptional J.E. J. T. R. Allis C.D. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). of the is for in a genetic histone modification and transcriptional R. Allis C.D. J. 1997; PubMed Scopus Google Scholar). a has been this is to R. L. Cell. Biol. 1996; PubMed Scopus Google Scholar, L. C. C. R. J. Allis C.D. Cell. Biol. 1997; 17: PubMed Google Scholar). yeast histone at and histone at lysines and J.E. Allis C.D. Nature. 1996; PubMed Scopus Google Scholar). the that in the activity on and studies at and that a with R. Allis C.D. J. 1997; PubMed Scopus Google J. L. J. 1994; PubMed Scopus Google Scholar, J. L. Cell. Biol. 1995; PubMed Google Scholar, T. G. Genet. 1995; PubMed Scopus Google Scholar). of to the of the transcriptional and in a by of J. L. Proc. Natl. Acad. Sci. U. S. A. 1994; PubMed Scopus Google R. L. P. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). and of or histone acetyltransferases have in the past is a histone on the of to and yeast J. Y. Nature. 1996; PubMed Scopus Google Scholar), with the transcriptional has activity for histones and but is also to histone is a histone with in to the acetyltransferases V. V. Y. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T. Nature. 1996; PubMed Scopus Google Scholar). is in that core histones in or in the acetylation on histone occurs at lysines and the that to acetylation in J. Y. Nature. 1996; PubMed Scopus Google Scholar). and to with transcription by and and also for the (for a review see R. T. Nature. 1996; PubMed Scopus Google Scholar). histones of in to yeast and and proteins a of by a of that a and a to and acetyltransferases C. J. A. L. Genet. 1996; PubMed Scopus Google Scholar, J. R. C. D. S. A.E. Genet. 1996; PubMed Scopus Google Scholar, J. T. D. G. 1996; PubMed Scopus Google Scholar, A. D. A. J. J. 1997; PubMed Scopus Google Scholar). or of proteins in transcriptional and have not been in a of a of with that the acetylation of histones or proteins J. R. C. D. S. A.E. Genet. 1996; PubMed Scopus Google Scholar). of or histone acetyltransferases have in the past is a histone on the of to and yeast J. Y. Nature. 1996; PubMed Scopus Google Scholar), with the transcriptional has activity for histones and but is also to histone is a histone with in to the acetyltransferases V. V. Y. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T. Nature. 1996; PubMed Scopus Google Scholar). is in that core histones in or in the acetylation on histone occurs at lysines and the that to acetylation in J. Y. Nature. 1996; PubMed Scopus Google Scholar). and to with transcription by and and also for the (for a review see R. T. Nature. 1996; PubMed Scopus Google Scholar). histones of in to yeast and and proteins a of by a of that a and a to and acetyltransferases C. J. A. L. Genet. 1996; PubMed Scopus Google Scholar, J. R. C. D. S. A.E. Genet. 1996; PubMed Scopus Google Scholar, J. T. D. G. 1996; PubMed Scopus Google Scholar, A. D. A. J. J. 1997; PubMed Scopus Google Scholar). or of proteins in transcriptional and have not been in a of a of with that the acetylation of histones or proteins J. R. C. D. S. A.E. Genet. 1996; PubMed Scopus Google Scholar). the general transcription of and the associated has been to a the or in the has a activity for of and a activity R. S. R. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T. J.E. T. Workman J.L. T. Y. C.D. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). histone over and has or activity on histones T. J.E. T. Workman J.L. T. Y. C.D. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). of for activity to the and to of activity in that nucleosomes over core the of the activity to for nucleosome of and a histone that as a histone as a for DNA with the core histones A. T. X. Y. R. Nature. 1996; PubMed Scopus Google Scholar, Y. S. M. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, X. T. A. R. Y. Nature. 1996; PubMed Scopus Google Scholar). the general transcription of and the associated has been to a the or in the has a activity for of and a activity R. S. R. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T. J.E. T. Workman J.L. T. Y. C.D. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). histone over and has or activity on histones T. J.E. T. Workman J.L. T. Y. C.D. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). of for activity to the and to of activity in that nucleosomes over core the of the activity to for nucleosome of and a histone that as a histone as a for DNA with the core histones A. T. X. Y. R. Nature. 1996; PubMed Scopus Google Scholar, Y. S. M. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, X. T. A. R. Y. Nature. 1996; PubMed Scopus Google Scholar). Histone with the identification of studies of histone in have also with the a in the and of a J. 1996; PubMed Scopus Google Scholar) of a Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar), and a associated of the to yeast to for repression and of a of M. R. Cell. Biol. PubMed Google Scholar). of in of of the histone as and Grunstein M. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, R. S. Grunstein M. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google from the of the of the and and to of histones and in the of as repression of R. S. Grunstein M. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar). of a of of that of as a histone to gene D. S. D. G. K. P. Nature. 1996; PubMed Scopus Google Scholar). findings to the acetylation of histone at is for transcriptional in yeast M. Allis C.D. B.M. Cell. Biol. 1996; PubMed Google Scholar) and is also associated with in B.M. J. Cell. 1992; Full Text PDF PubMed Google Scholar), net in with the of histone in transcriptional repression is the of the DNA in cell and with and with a transcriptional linked to yeast Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, C.D. E. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). studies also associated with and histone in cell Y. R. P. D. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). a transcription that as a repressor to histone C. Y. D. E. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar), and and for with and histone L. R. J. L. D. Nature. 1997; PubMed Google Scholar, T. T.M. M. 1997; PubMed Google Scholar, L. D. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). of by the yeast also of a and D. K. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). This of for a of repression by the of histone to with the identification of studies of histone in have also with the a in the and of a J. 1996; PubMed Scopus Google Scholar) of a Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar), and a associated of the to yeast to for repression and of a of M. R. Cell. Biol. PubMed Google Scholar). of in of of the histone as and Grunstein M. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, R. S. Grunstein M. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar). from the of the of the and and to of histones and in the of as repression of R. S. Grunstein M. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar). of a of of that of as a histone to gene D. S. D. G. K. P. Nature. 1996; PubMed Scopus Google Scholar). findings to the acetylation of histone at is for transcriptional in yeast M. Allis C.D. B.M. Cell. Biol. 1996; PubMed Google Scholar) and is also associated with in B.M. J. Cell. 1992; Full Text PDF PubMed Google Scholar), net in with the of histone in transcriptional repression is the of the DNA in cell and with and with a transcriptional linked to yeast Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, C.D. E. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). studies also associated with and histone in cell Y. R. P. D. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). a transcription that as a repressor to histone C. Y. D. E. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar), and and for with and histone L. R. J. L. D. Nature. 1997; PubMed Google Scholar, T. T.M. M. 1997; PubMed Google Scholar, L. D. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). of by the yeast also of a and D. K. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). This of for a of repression by the of histone to the of so of chromatin structure a of that for is the of histones during the histones or from and how a structure interactions DNA S. M. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google nucleosomes that or to the structure of DNA have for in chromatin by proteins as and Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar) and by the L. A. D. M. Cell. 1997; Full Text Full Text PDF PubMed Google chromatin for a gene and at of the the of regulators, of the or activities to specific or the chromatin of for by is the of the modification a nucleosome and how is the modification the activities of the histone acetyltransferases and histone with the of nucleosome on higher order chromatin or is by higher order chromatin to and not only for the of gene but also for of the of so of chromatin structure a of that for is the of histones during the histones or from and how a structure interactions DNA S. M. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Scopus Google nucleosomes that or to the structure of DNA have for in chromatin by proteins as and Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar) and by the L. A. D. M. Cell. 1997; Full Text Full Text PDF PubMed Google chromatin for a gene and at of the the of regulators, of the or activities to specific or the chromatin of for by is the of the modification a nucleosome and how is the modification the activities of the histone acetyltransferases and histone with the of nucleosome on higher order chromatin or is by higher order chromatin to and not only for the of gene but also for of colleagues of in and for in this