Histone deacetylases and phosphorylated polymerase II C-terminal domain recruit Spt6 for cotranscriptional histone reassembly

Mol Cell Biol. 2014 Nov 15;34(22):4115-29. doi: 10.1128/MCB.00695-14. Epub 2014 Sep 2.


Spt6 is a multifunctional histone chaperone involved in the maintenance of chromatin structure during elongation by RNA polymerase II (Pol II). Spt6 has a tandem SH2 (tSH2) domain within its C terminus that recognizes Pol II C-terminal domain (CTD) peptides phosphorylated on Ser2, Ser5, or Try1 in vitro. Deleting the tSH2 domain, however, only has a partial effect on Spt6 occupancy in vivo, suggesting that more complex mechanisms are involved in the Spt6 recruitment. Our results show that the Ser2 kinases Bur1 and Ctk1, but not the Ser5 kinase Kin28, cooperate in recruiting Spt6, genome-wide. Interestingly, the Ser2 kinases promote the association of Spt6 in early transcribed regions and not toward the 3' ends of genes, where phosphorylated Ser2 reaches its maximum level. In addition, our results uncover an unexpected role for histone deacetylases (Rpd3 and Hos2) in promoting Spt6 interaction with elongating Pol II. Finally, our data suggest that phosphorylation of the Pol II CTD on Tyr1 promotes the association of Spt6 with the 3' ends of transcribed genes, independently of Ser2 phosphorylation. Collectively, our results show that a complex network of interactions, involving the Spt6 tSH2 domain, CTD phosphorylation, and histone deacetylases, coordinate the recruitment of Spt6 to transcribed genes in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin-Dependent Kinases / metabolism
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Histone Chaperones
  • Histone Deacetylases / metabolism*
  • Histones / metabolism*
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Interaction Maps
  • Protein Kinases / metabolism
  • Protein Structure, Tertiary
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription, Genetic
  • Transcriptional Elongation Factors / metabolism*


  • CTDK-I protein complex, S cerevisiae
  • Histone Chaperones
  • Histones
  • Nuclear Proteins
  • SPT6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors
  • Protein Kinases
  • Cyclin-Dependent Kinases
  • SGV1 protein, S cerevisiae
  • RNA Polymerase II
  • HOS2 protein, S cerevisiae
  • RPD3 protein, S cerevisiae
  • Histone Deacetylases