A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme.

The elongator complex is a major component of the RNA polymerase II (RNAPII) holoenzyme responsible for transcriptional elongation in yeast. Here we identify Elp3, the 60-kilodalton subunit of elongator/RNAPII holoenzyme, as a highly conserved histone acetyltransferase (HAT) capable of acetylating core histones in vitro. In vivo, ELP3 gene deletion confers typical elp phenotypes such as slow growth adaptation, slow gene activation, and temperature sensitivity. These results suggest a role for a novel, tightly RNAPII-associated HAT in transcription of DNA packaged in chromatin.

[1]  D. Edmondson,et al.  Repression domain of the yeast global repressor Tup1 interacts directly with histones H3 and H4. , 1996, Genes & development.

[2]  C. Allis,et al.  Tetrahymena Histone Acetyltransferase A: A Homolog to Yeast Gcn5p Linking Histone Acetylation to Gene Activation , 1996, Cell.

[3]  B. Barrell,et al.  Life with 6000 Genes , 1996, Science.

[4]  K. Yano,et al.  DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. , 1998, Genes & development.

[5]  P. Chambon,et al.  Transcription by eukaryotic RNA polymerases A and B of chromatin assembled in vitro. , 1979, European journal of biochemistry.

[6]  A. Travers.  The reprogramming of transcriptional competence , 1992, Cell.

[7]  P. Højrup,et al.  Use of mass spectrometric molecular weight information to identify proteins in sequence databases. , 1993, Biological mass spectrometry.

[8]  D. Landsman,et al.  GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein. , 1997, Trends in biochemical sciences.

[9]  C. Allis,et al.  Roles of histone acetyltransferases and deacetylases in gene regulation , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[10]  G. Schroth,et al.  Studies of the DNA binding properties of histone H4 amino terminus. Thermal denaturation studies reveal that acetylation markedly reduces the binding constant of the H4 "tail" to DNA. , 1993, The Journal of biological chemistry.

[11]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[12]  D. Landsman,et al.  The Biochemical and Phenotypic Characterization of Hho1p, the Putative Linker Histone H1 of Saccharomyces cerevisiae * , 1998, The Journal of Biological Chemistry.

[13]  F. Winston,et al.  Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. , 1998, Genes & development.

[14]  M. Grunstein,et al.  Effects of histone H4 depletion on the cell cycle and transcription of Saccharomyces cerevisiae. , 1988, The EMBO journal.

[15]  J. Davie,et al.  Histone Acetylation Is Required to Maintain the Unfolded Nucleosome Structure Associated with Transcribing DNA* , 1998, The Journal of Biological Chemistry.

[16]  M. Grunstein,et al.  Nucleosome loss activates yeast downstream promoters in vivo , 1988, Cell.

[17]  Stephen K. Burley,et al.  Crystal Structure of a GCN5-Related N-acetyltransferase Serratia marcescens Aminoglycoside 3-N-acetyltransferase , 1998, Cell.

[18]  C. Allis,et al.  Special HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation. , 1996, Current opinion in genetics & development.

[19]  C. D. Allis,et al.  Linking histone acetylation to transcriptional regulation , 1998, Cellular and Molecular Life Sciences CMLS.

[20]  A. Wolffe,et al.  The nucleosome: a powerful regulator of transcription. , 1998, Progress in nucleic acid research and molecular biology.

[21]  Xuetong Shen,et al.  Linker histories are not essential and affect chromatin condensation in vivo , 1995, Cell.

[22]  R. Conaway,et al.  The RNA polymerase II general elongation factors. , 1996, Trends in biochemical sciences.

[23]  G. Orphanides,et al.  FACT, a Factor that Facilitates Transcript Elongation through Nucleosomes , 1998, Cell.

[24]  C. Allis,et al.  An activity gel assay detects a single, catalytically active histone acetyltransferase subunit in Tetrahymena macronuclei. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Sternglanz,et al.  Structure of the Histone Acetyltransferase Hat1 A Paradigm for the GCN5-Related N-acetyltransferase Superfamily , 1998, Cell.

[26]  H. Erdjument-Bromage,et al.  Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. , 1999, Molecular cell.

[27]  G. Orphanides,et al.  A Human RNA Polymerase II Complex Containing Factors That Modify Chromatin Structure , 1998, Molecular and Cellular Biology.

[28]  Xuetong Shen,et al.  Linker Histone H1 Regulates Specific Gene Expression but Not Global Transcription In Vivo , 1996, Cell.

[29]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[30]  C. Allis,et al.  Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo. , 1998, Genes & development.

[31]  R. Roeder,et al.  The role of general initiation factors in transcription by RNA polymerase II. , 1996, Trends in biochemical sciences.

[32]  J. R. Davie,et al.  Histone modifications in the yeast S. Cerevisiae , 1981, Nucleic Acids Res..

[33]  S. Carr,et al.  Examination of micro-tip reversed-phase liquid chromatographic extraction of peptide pools for mass spectrometric analysis. , 1998, Journal of chromatography. A.

[34]  Andreas Hecht,et al.  Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: A molecular model for the formation of heterochromatin in yeast , 1995, Cell.

[35]  H. Erdjument-Bromage,et al.  Methodical analysis of protein-nitrocellulose interactions to design a refined digestion protocol. , 1996, Analytical biochemistry.

[36]  A. Mirzabekov,et al.  Change in the pattern of histone binding to DNA upon transcriptional activation , 1989, Cell.

[37]  Rodney Rothstein,et al.  Elevated recombination rates in transcriptionally active DNA , 1989, Cell.

[38]  Alan P. Wolffe,et al.  Disruption of Higher-Order Folding by Core Histone Acetylation Dramatically Enhances Transcription of Nucleosomal Arrays by RNA Polymerase III , 1998, Molecular and Cellular Biology.

[39]  D. Luse,et al.  Transcription on nucleosomal templates by RNA polymerase II in vitro: inhibition of elongation with enhancement of sequence-specific pausing. , 1991, Genes & development.

[40]  T. R. Hebbes,et al.  Core histone hyperacetylation co‐maps with generalized DNase I sensitivity in the chicken beta‐globin chromosomal domain. , 1994, The EMBO journal.