All Publications


  • Set5 and Set1 cooperate to repress gene expression at telomeres and retrotransposons. Epigenetics Martín, G. M., King, D. A., Green, E. M., Garcia-Nieto, P. E., Alexander, R., Collins, S. R., Krogan, N. J., Gozani, O. P., Morrison, A. J. 2014; 9 (4): 513-522

    Abstract

    A complex interplay between multiple chromatin modifiers is critical for cells to regulate chromatin structure and accessibility during essential DNA-templated processes such as transcription. However, the coordinated activities of these chromatin modifiers in the regulation of gene expression are not fully understood. We previously determined that the budding yeast histone H4 methyltransferase Set5 functions together with Set1, the H3K4 methyltransferase, in specific cellular contexts. Here, we sought to understand the relationship between these evolutionarily conserved enzymes in the regulation of gene expression. We generated a comprehensive genetic interaction map of the functionally uncharacterized Set5 methyltransferase and expanded the existing genetic interactome of the global chromatin modifier Set1, revealing functional overlap of the two enzymes in chromatin-related networks, such as transcription. Furthermore, gene expression profiling via RNA-Seq revealed an unexpected synergistic role of Set1 and Set5 in repressing transcription of Ty transposable elements and genes located in subtelomeric regions. This study uncovers novel pathways in which the methyltransferase Set5 participates and, more importantly, reveals a partnership between Set1 and Set5 in transcriptional repression near repetitive DNA elements in budding yeast. Together, our results define a new functional relationship between histone H3 and H4 methyltransferases, whose combined activity may be implicated in preserving genomic integrity.

    View details for DOI 10.4161/epi.27645

    View details for PubMedID 24442241

    View details for PubMedCentralID PMC4121362

  • Transcriptome profiling of Set5 and Set1 methyltransferases: Tools for visualization of gene expression Genomics Data Martín, G. M., King, D. A., Garcia-Nieto, P. E., Morrison, A. J. 2014; 2: 216-218

    Abstract

    Cells regulate transcription by coordinating the activities of multiple histone modifying complexes. We recently identified the yeast histone H4 methyltransferase Set5 and discovered functional overlap with the histone H3 methyltransferase Set1 in gene expression. Specifically, using next-generation RNA sequencing (RNA-Seq), we found that Set5 and Set1 function synergistically to regulate specific transcriptional programs at subtelomeres and transposable elements [1]. Here we provide a comprehensive description of the methodology and analysis tools corresponding to the data deposited in NCBI's Gene Expression Omnibus (GEO) under the accession number GSE52086. This data complements the experimental methods described in Mas Martín G et al., 2014, and provides the means to explore the cooperative functions of histone H3 and H4 methyltransferases in the regulation of transcription. Furthermore, a fully annotated R code is included to enable researchers to use the following computational tools: comparison of significant differential expression (SDE) profiles; gene ontology enrichment of SDE; and enrichment of SDE relative to chromosomal features, such as centromeres, telomeres, and transposable elements. Overall, we present a bioinformatics platform that can be generally implemented for similar analyses with different datasets and in different organisms.

    View details for DOI 10.1016/j.gdata.2014.07.001

    View details for PubMedCentralID PMC4140983