Set5 and Set1 cooperate to repress gene expression at telomeres and retrotransposons.
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.
Department of Biology; Stanford University; Stanford, CA USA.
Glòria Mas
GM
Martín
Department of Biology; Stanford University; Stanford, CA USA.
Devin A
DA
King
Department of Biology; Stanford University; Stanford, CA USA.
Erin M
EM
Green
Department of Biology; Stanford University; Stanford, CA USA.
Pablo E
PE
Garcia-Nieto
Department of Cellular and Molecular Pharmacology; University of California San Francisco; San Francisco, CA USA.
Richard
R
Alexander
Department of Chemical and Systems Biology; Stanford University; Stanford, CA USA.
Sean R
SR
Collins
Department of Cellular and Molecular Pharmacology; University of California San Francisco; San Francisco, CA USA.
Nevan J
NJ
Krogan
Department of Biology; Stanford University; Stanford, CA USA.
Or P
OP
Gozani
Department of Biology; Stanford University; Stanford, CA USA.
Ashby J
AJ
Morrison
D002843:Chromatin / Q000378:metabolism; D015870:Gene Expression; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D018626:Retroelements; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D018626:Retroelements; D029701:Saccharomyces cerevisiae Proteins; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; C000593293:Set-5 protein, S cerevisiae
Set1; Set5; genetic interaction; histone methylation; retrotransposons; telomeres; transcription