title: Genomic insights of protein arginine methyltransferase Hmt1 binding reveals novel regulatory functions.
abstract: BACKGROUND
  Protein arginine methylation is a post-translational modification involved in important biological processes such as transcription and RNA processing. This modification is catalyzed by both type I and II protein arginine methyltransferases (PRMTs). One of the most conserved type I PRMTs is PRMT1, the homolog of which is Hmt1 in Saccharomyces cerevisiae. Hmt1 has been shown to play a role in various gene expression steps, such as promoting the dynamics of messenger ribonucleoprotein particle (mRNP) biogenesis, pre-mRNA splicing, and silencing of chromatin. To determine the full extent of Hmt1's involvement during gene expression, we carried out a genome-wide location analysis for Hmt1.
  
  
  RESULTS
  A comprehensive genome-wide binding profile for Hmt1 was obtained by ChIP-chip using NimbleGen high-resolution tiling microarrays. Of the approximately 1000 Hmt1-binding sites found, the majority fall within or proximal to an ORF. Different occupancy patterns of Hmt1 across genes with different transcriptional rates were found. Interestingly, Hmt1 occupancy is found at a number of other genomic features such as tRNA and snoRNA genes, thereby implicating a regulatory role in the biogenesis of these non-coding RNAs. RNA hybridization analysis shows that Hmt1 loss-of-function mutants display higher steady-state tRNA abundance relative to the wild-type. Co-immunoprecipitation studies demonstrate that Hmt1 interacts with the TFIIIB component Bdp1, suggesting a mechanism for Hmt1 in modulating RNA Pol III transcription to regulate tRNA production.
  
  
  CONCLUSIONS
  The genome-wide binding profile of Hmt1 reveals multiple potential new roles for Hmt1 in the control of eukaryotic gene expression, especially in the realm of non-coding RNAs. The data obtained here will provide an important blueprint for future mechanistic studies on the described occupancy relationship for genomic features bound by Hmt1.
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Milliman
authors.forename: Zihua
authors.initials: Z
authors.lastname: Hu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Yu
mesh_terms: D055162:Biocatalysis; D023281:Genomics; D009154:Mutation; D059372:Nucleotide Motifs; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames / Q000235:genetics; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000235:genetics; D012343:RNA, Transfer / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D035361:Transcription Factor TFIIIB / Q000378:metabolism
chemical_list: C474805:Bdp1 protein, S cerevisiae; D020537:RNA, Small Nucleolar; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D035361:Transcription Factor TFIIIB; D012343:RNA, Transfer; C475182:HMT1 protein, S cerevisiae; D011484:Protein-Arginine N-Methyltransferases