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Vol 47(2013) N 5 p. 655-667;
O.I. Kulaeva2, N.V. Maluchenko1, D.V. Nikitin1, A.V. Demidenko1, O.V. Chertkov1, N.S. Efimova1, M.P. Kirpichnikov1, V.M. Studitsky2*

Molecular Mechanisms of Transcription through a Nucleosome by RNA Polymerase II

1Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA
2Biological Faculty, Moscow State University, Moscow, 119991, Russia

*vasily.studitsky@fccc.edu
Received - 2013-04-30; Accepted - 2013-04-30

The RNA polymerase II (Pol II)-type mechanism is conserved from yeast to human. After transcription initiation, Pol II usually pauses upstream of or in a nucleosome within the early transcribed region of a gene. Then Pol II overcomes the initial nucleosomal barrier and efficiently proceeds through chromatin. At a low to moderate transcription rate, Pol II progression is only characterized by displacement or exchange of H2A/H2B dimers, and the resulting hexasomes (subnucleosomes lacking one of the H2A/H2B dimers) survive owing to the formation of small intranucleosomal DNA loops. The nucleosome structure is restored before the next Pol II complex starts transcription at a moderate transcription rate. The mechanism most likely helps to preserve the histone code during transcription. As the transcription rate increases, the distance between transcribing Pol II complexes becomes shorter, and trailing Pol II complexes may encounter the hexasome formed in the previous transcription round before the H2A/H2B dimer rebinds to it to restore a complete nucleosome. An unstable intermediate with fewer DNA-histone contacts forms in this case, resulting in the eviction or exchange of all core histones during transcription. Various protein factors and histone chaperones are involved in chromatin transcription by Pol II in vivo.

chromatin, transcription, nucleosome, nucleosomal barrier, RNA polymerase II, FACT



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