Structural highlights
Function
SPT6_YEAST Plays a role in maintenance of chromatin structure during RNA polymerase II transcription elongation thereby repressing transcription initiation from cryptic promoters. Mediates the reassembly of nucleosomes onto the promoters of at least a selected set of genes during repression; the nucleosome reassembly is essential for transcriptional repression. Essential for viability.[1] [2] [3] [4]
Publication Abstract from PubMed
We determined that the tandem SH2 domain of S. cerevisiae Spt6 binds the linker region of the RNA polymerase II subunit Rpb1 rather than the expected sites in its heptad repeat domain. The 4 nM binding affinity requires phosphorylation at Rpb1 S1493 and either T1471 or Y1473. Crystal structures showed that pT1471 binds the canonical SH2 pY site while pS1493 binds an unanticipated pocket 70 A distant. Remarkably, the pT1471 phosphate occupies the phosphate-binding site of a canonical pY complex, while Y1473 occupies the position of a canonical pY side chain, with the combination of pT and Y mimicking a pY moiety. Biochemical data and modeling indicate that pY1473 can form an equivalent interaction, and we find that pT1471/pS1493 and pY1473/pS1493 combinations occur in vivo. ChIP-seq and genetic analyses demonstrate the importance of these interactions for recruitment of Spt6 to sites of transcription and for the maintenance of repressive chromatin.
A novel SH2 recognition mechanism recruits Spt6 to the doubly phosphorylated RNA polymerase II linker at sites of transcription.,Sdano MA, Fulcher JM, Palani S, Chandrasekharan MB, Parnell TJ, Whitby FG, Formosa T, Hill CP Elife. 2017 Aug 16;6. pii: e28723. doi: 10.7554/eLife.28723. PMID:28826505[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hartzog GA, Wada T, Handa H, Winston F. Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. Genes Dev. 1998 Feb 1;12(3):357-69. PMID:9450930
- ↑ Kaplan CD, Laprade L, Winston F. Transcription elongation factors repress transcription initiation from cryptic sites. Science. 2003 Aug 22;301(5636):1096-9. PMID:12934008 doi:http://dx.doi.org/10.1126/science.1087374
- ↑ Kaplan CD, Holland MJ, Winston F. Interaction between transcription elongation factors and mRNA 3'-end formation at the Saccharomyces cerevisiae GAL10-GAL7 locus. J Biol Chem. 2005 Jan 14;280(2):913-22. Epub 2004 Nov 5. PMID:15531585 doi:http://dx.doi.org/10.1074/jbc.M411108200
- ↑ Adkins MW, Tyler JK. Transcriptional activators are dispensable for transcription in the absence of Spt6-mediated chromatin reassembly of promoter regions. Mol Cell. 2006 Feb 3;21(3):405-16. PMID:16455495 doi:http://dx.doi.org/S1097-2765(05)01852-6
- ↑ Sdano MA, Fulcher JM, Palani S, Chandrasekharan MB, Parnell TJ, Whitby FG, Formosa T, Hill CP. A novel SH2 recognition mechanism recruits Spt6 to the doubly phosphorylated RNA polymerase II linker at sites of transcription. Elife. 2017 Aug 16;6. pii: e28723. doi: 10.7554/eLife.28723. PMID:28826505 doi:http://dx.doi.org/10.7554/eLife.28723
