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. 2016;2(2):8.
doi: 10.21767/2471-8084.100017. Epub 2016 May 30.

Nucleosomal Barrier to Transcription: Structural Determinants and Changes in Chromatin Structure

Vasily M Studitsky  1 , Ekaterina V Nizovtseva  2 , Alexey K Shaytan  3 , Donal S Luse  4
Affiliations

Nucleosomal Barrier to Transcription: Structural Determinants and Changes in Chromatin Structure

Vasily M Studitsky et al. Biochem Mol Biol J. 2016.

Abstract

Packaging of DNA into chromatin affects all processes on DNA. Nucleosomes present a strong barrier to transcription, raising important questions about the nature and the mechanisms of overcoming the barrier. Recently it was shown that DNA sequence, DNA-histone interactions and backtracking by RNA polymerase II (Pol II) all contribute to formation of the barrier. After partial uncoiling of nucleosomal DNA from histone octamer by Pol II and backtracking of the enzyme, nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. Histone chaperones and transcription factors TFIIS, TFIIF and FACT facilitate transcription through chromatin using different molecular mechanisms.

Keywords: RNA polymerase II; arrest; chromatin; elongation; intermediates; mechanism; nucleosome; pausing; structure; transcription.

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Figures

Figure 1
Figure 1. Structures of intermediates and the minimal kinetic scheme of Pol II transcription through the nucleosomal barrier
As Pol II enters a nucleosome (intermediate 1), it pauses and can backtrack along DNA (1.1). Backtracked state is strongly stabilized by recoiling of DNA on the open histone octamer surface (1.2). Bulk of Pol II collides with nucleosomal DNA, forming a very tight complex that strongly inhibits recovery of Pol II from the backtracked state. Pol II can recover from arrest with help of TFIIS that facilitates Pol II-induced RNA cleavage, providing Pol II with another chance to proceed further in the nucleosome, accompanied by uncoiling of nucleosomal DNA and facilitated by transient, stepwise binding of histone chaperone FACT to H2A/H2B dimers (2). Insert: A model of yeast RNA polymerase II elongation complex (PDB 1Y1W) with the active center at the position +42 bp in the nucleosome (PDB 1KX5). The model was built using the published structure of the +42 complex with E. coli RNA polymerase [18] where the bacterial enzyme was replaced by Pol II. Dotted line indicates direction of transcription by Pol II.
See this image and copyright information in PMC

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