7o3d

Cooperation between the intrinsically disordered and ordered regions of Spt6 regulates nucleosome and Pol II CTD binding, and nucleosome assemblyCooperation between the intrinsically disordered and ordered regions of Spt6 regulates nucleosome and Pol II CTD binding, and nucleosome assembly

Structural highlights

7o3d is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Transcription elongation factor Spt6 associates with RNA polymerase II (Pol II) and acts as a histone chaperone, which promotes the reassembly of nucleosomes following the passage of Pol II. The precise mechanism of nucleosome reassembly mediated by Spt6 remains unclear. In this study, we used a hybrid approach combining cryo-electron microscopy and small-angle X-ray scattering to visualize the architecture of Spt6 from Saccharomyces cerevisiae. The reconstructed overall architecture of Spt6 reveals not only the core of Spt6, but also its flexible N- and C-termini, which are critical for Spt6's function. We found that the acidic N-terminal region of Spt6 prevents the binding of Spt6 not only to the Pol II CTD and Pol II CTD-linker, but also to pre-formed intact nucleosomes and nucleosomal DNA. The N-terminal region of Spt6 self-associates with the tSH2 domain and the core of Spt6 and thus controls binding to Pol II and nucleosomes. Furthermore, we found that Spt6 promotes the assembly of nucleosomes in vitro. These data indicate that the cooperation between the intrinsically disordered and structured regions of Spt6 regulates nucleosome and Pol II CTD binding, and also nucleosome assembly.

Cooperation between intrinsically disordered and ordered regions of Spt6 regulates nucleosome and Pol II CTD binding, and nucleosome assembly.,Kasiliauskaite A, Kubicek K, Klumpler T, Zanova M, Zapletal D, Koutna E, Novacek J, Stefl R Nucleic Acids Res. 2022 Jun 10;50(10):5961-5973. doi: 10.1093/nar/gkac451. PMID:35640611^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Kasiliauskaite A, Kubicek K, Klumpler T, Zanova M, Zapletal D, Koutna E, Novacek J, Stefl R. Cooperation between intrinsically disordered and ordered regions of Spt6 regulates nucleosome and Pol II CTD binding, and nucleosome assembly. Nucleic Acids Res. 2022 Jun 10;50(10):5961-5973. doi: 10.1093/nar/gkac451. PMID:35640611 doi:http://dx.doi.org/10.1093/nar/gkac451

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OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] Kasiliauskaite A, Kubicek K, Klumpler T, Zanova M, Zapletal D, Koutna E, Novacek J, Stefl R. Cooperation between intrinsically disordered and ordered regions of Spt6 regulates nucleosome and Pol II CTD binding, and nucleosome assembly. Nucleic Acids Res. 2022 Jun 10;50(10):5961-5973. doi: 10.1093/nar/gkac451. PMID:35640611 doi:http://dx.doi.org/10.1093/nar/gkac451

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