Evidence for Regulation of ECM3 Expression by Methylation of Histone H3 Lysine 4 and Intergenic Transcription in Saccharomyces cerevisiae.

Transcription of nonprotein-coding DNA is widespread in eukaryotes and plays important regulatory roles for many genes, including genes that are misregulated in cancer cells. Its pervasiveness presents the potential for a wealth of diverse regulatory roles for noncoding transcription. We previously showed that the act of transcribing noncoding DNA (ncDNA) across the promoter of the protein-coding SER3 gene in Saccharomyces cerevisiae positions nucleosomes over the upstream activating sequences, leading to strong repression of SER3 transcription.

Regulation of chaperone binding and nucleosome dynamics by key residues within the globular domain of histone H3.

Background: Nucleosomes have an important role in modulating access of DNA by regulatory factors. The role specific histone residues have in this process has been shown to be an important mechanism of transcription regulation. Previously, we identified eight amino acids in histones H3 and H4 that are required for nucleosome occupancy over highly transcribed regions of the genome.

Identification of Mutant Versions of the Spt16 Histone Chaperone That Are Defective for Transcription-Coupled Nucleosome Occupancy in Saccharomyces cerevisiae.

The highly conserved FACT (Facilitates Chromatin Transactions) complex performs essential functions in eukaryotic cells through the reorganization of nucleosomes. During transcription, FACT reorganizes nucleosomes to allow passage of RNA Polymerase II and then assists in restoring these nucleosomes after RNA Polymerase II has passed. We have previously shown, consistent with this function, that Spt16 facilitates repression of the Saccharomyces cerevisiae SER3 gene by maintaining nucleosome occupancy over the promoter of this gene as a consequence of intergenic transcription of SRG1 noncoding DNA.

The Paf1 complex represses SER3 transcription in Saccharomyces cerevisiae by facilitating intergenic transcription-dependent nucleosome occupancy of the SER3 promoter.

Previous studies have shown that repression of the Saccharomyces cerevisiae SER3 gene is dependent on transcription of SRG1 from noncoding DNA initiating within the intergenic region 5' of SER3 and extending across the SER3 promoter region. By a mechanism dependent on the activities of the Swi/Snf chromatin remodeling factor, the HMG-like factor Spt2, and the Spt6 and Spt16 histone chaperones, SRG1 transcription deposits nucleosomes over the SER3 promoter to prevent transcription factors from binding and activating SER3. In this study, we uncover a role for the Paf1 transcription elongation complex in SER3 repression.

Transcription of ncDNA: Many roads lead to local gene regulation.

Transcription of ncDNA occurs throughout eukaryotic genomes, generating a wide array of ncRNAs. One large class of ncRNAs includes those transcribed over the promoter regions of nearby protein coding genes. Recent studies, primarily focusing on individual genes have uncovered multiple mechanisms by which promoter-associated transcriptional activity locally alters gene expression.

Identification of histone mutants that are defective for transcription-coupled nucleosome occupancy.

Our previous studies of Saccharomyces cerevisiae described a gene repression mechanism where the transcription of intergenic noncoding DNA (ncDNA) (SRG1) assembles nucleosomes across the promoter of the adjacent SER3 gene that interfere with the binding of transcription factors. To investigate the role of histones in this mechanism, we screened a comprehensive library of histone H3 and H4 mutants for those that derepress SER3. We identified mutations altering eight histone residues (H3 residues V46, R49, V117, Q120, and K122 and H4 residues R36, I46, and S47) that strongly increase SER3 expression without reducing the transcription of the intergenic SRG1 ncDNA.

Transcription of intergenic DNA deposits nucleosomes on promoter to silence gene expression.

Comment on: Hainer SJ, et al. Genes Dev. 2011; 25:29-40

Intergenic transcription causes repression by directing nucleosome assembly.

Transcription of non-protein-coding DNA (ncDNA) and its noncoding RNA (ncRNA) products are beginning to emerge as key regulators of gene expression. We previously identified a regulatory system in Saccharomyces cerevisiae whereby transcription of intergenic ncDNA (SRG1) represses transcription of an adjacent protein-coding gene (SER3) through transcription interference. We now provide evidence that SRG1 transcription causes repression of SER3 by directing a high level of nucleosomes over SRG1, which overlaps the SER3 promoter.

Regulation of an intergenic transcript controls adjacent gene transcription in Saccharomyces cerevisiae.

Recent studies have revealed that transcription of noncoding, intergenic DNA is abundant among eukaryotes. However, the functions of this transcription are poorly understood. We have previously shown that in Saccharomyces cerevisiae, expression of an intergenic transcript, SRG1, represses the transcription of the adjacent gene, SER3, by transcription interference.

Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene.

Transcription by RNA polymerase II in Saccharomyces cerevisiae and in humans is widespread, even in genomic regions that do not encode proteins. The purpose of such intergenic transcription is largely unknown, although it can be regulatory. We have discovered a role for one case of intergenic transcription by studying the S.

Recent advances in understanding chromatin remodeling by Swi/Snf complexes.

Members of the Swi/Snf family of chromatin-remodeling complexes play critical roles in transcriptional control. Recent studies have made significant advances in our understanding of the fundamental aspects of Swi/Snf complexes, including the roles of specific subunits, the repression of transcription, and the mechanism of remodeling. In addition, new findings also indicate an important role for the Swi/Snf-related complex, RSC, in controlling gene expression.

Evidence that Swi/Snf directly represses transcription in S. cerevisiae.

Many studies have established that the Swi/Snf family of chromatin-remodeling complexes activate transcription. Recent reports have suggested the possibility that these complexes can also repress transcription. We now present chromatin immunoprecipitation evidence that the Swi/Snf complex of Saccharomyces cerevisiae directly represses transcription of the SER3 gene.