Structure–function studies of histone H3/H4 tetramer maintenance during transcription by chaperone Spt2 Journal Article
| Authors: | Chen, S.; Rufiange, A.; Huang, H.; Rajashankar, K. R.; Nourani, A.; Patel, D. J. |
| Article Title: | Structure–function studies of histone H3/H4 tetramer maintenance during transcription by chaperone Spt2 |
| Abstract: | Cells use specific mechanisms such as histone chaperones to abrogate the inherent barrier that the nucleosome poses to transcribing polymerases. The current model postulates that nucleosomes can be transiently disrupted to accommodate passage of RNA polymerases and that histones H3 and H4 possess their own chaperones dedicated to the recovery of nucleosomes. Here, we determined the crystal structure of the conserved C terminus of human Suppressors of Ty insertions 2 (hSpt2C) chaperone bound to an H3/H4 tetramer. The structural studies demonstrate that hSpt2C is bound to the periphery of the H3/H4 tetramer, mimicking the trajectory of nucleosomal-bound DNA. These structural studies have been complemented with in vitro binding and in vivo functional studies on mutants that disrupt key intermolecular contacts involving two acidic patches and hydrophobic residues on Spt2C. We show that contacts between both human and yeast Spt2C with the H3/H4 tetramer are required for the suppression of H3/ H4 exchange as measured by H3K56ac and new H3 deposition. These interactions are also crucial for the inhibition of spurious transcription from within coding regions. Together, our data indicate that Spt2 interacts with the periphery of the H3/H4 tetramer and promotes its recycling in the wake of RNA polymerase. © 2015, Chen et al. |
| Keywords: | controlled study; protein expression; unclassified drug; promoter region; nonhuman; binding affinity; protein function; complex formation; carboxy terminal sequence; structure activity relation; epigenetics; histone h3; crystal structure; hydrogen bond; protein structure; molecular weight; tetramer; chromatin structure; stoichiometry; transcription elongation; rna polymerase; chaperone; nucleosome; histone h4; h3; cross linking; light scattering; isothermal titration calorimetry; histone chaperone; human; priority journal; article; h4 tetramer; histone maintenance; spt2; spurious transcription; human suppressor of ty insertions 2 chaperone |
| Journal Title: | Genes and Development |
| Volume: | 29 |
| Issue: | 12 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2015-06-15 |
| Start Page: | 1326 |
| End Page: | 1340 |
| Language: | English |
| DOI: | 10.1101/gad.261115.115 |
| PROVIDER: | scopus |
| PMCID: | PMC4495402 |
| PUBMED: | 26109053 |
| DOI/URL: | |
| Notes: | Export Date: 3 August 2015 -- Source: Scopus |
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