Deciphering the roles of the histone H2B N-terminal domain in genome-wide transcription.
Histone N-terminal domains are frequent targets of posttranslational modifications. Multiple acetylated lysine residues have been identified in the N-terminal domain of H2B (K6, K11, K16, K17, K21, and K22), but little is known about how these modifications regulate transcription. We systematically mutated the N-terminal domain of histone H2B, both at known sites of lysine acetylation and elsewhere, and characterized the resulting changes in genome-wide expression in each mutant strain. Our results indicate that known sites of lysine acetylation in this domain are required for gene-specific transcriptional activation. However, the entire H2B N-terminal domain is principally required for the transcriptional repression of a large subset of the yeast genome. We find that the histone H2B repression (HBR) domain, comprised of residues 30 to 37, is necessary and sufficient for this repression. Many of the genes repressed by the HBR domain are located adjacent to telomeres or function in vitamin and carbohydrate metabolism. Deletion of the HBR domain also confers an increased sensitivity to DNA damage by UV irradiation. We mapped the critical residues in the HBR domain required for its repression function. Finally, comparisons of these data with previous studies reveal that a surprising number of genes are coregulated by the N-terminal domains of histone H2B, H3, and H4.
Parra
Michael A
MA
School of Molecular Biosciences, Washington State University, Fulmer Hall 675, Pullman, Washington 99164-4660, USA.
Kerr
David
D
Fahy
Deirdre
D
Pouchnik
Derek J
DJ
Wyrick
John J
JJ
D000107:Acetylation; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000528:radiation effects; D016681:Genome, Fungal; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D040081:Protein Array Analysis; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D013045:Species Specificity; D016615:Telomere / Q000235:genetics; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
D006657:Histones; D012097:Repressor Proteins; D008239:Lysine