Nucleic Acids Research Advance Access published online on July 13, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp574
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Gene Regulation, Chromatin and Epigenetics |
A translational signature for nucleosome positioning in vivo
1Fondazione Istituto Pasteur-Fondazione Cenci Bolognetti, c/o Dipartimento di Genetica e Biologia Molecolare, 2Istituto Biologia e Patologia Molecolari del Consiglio Nazionale delle Ricerche, Università La Sapienza, 00185 Rome, Italy, 3MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK and 4Fondation Pierre-Gilles de Gennes de la Recherche, c/o LBPA, École Normale Supérieure de Cachan, 94235 Cachan, France
*To whom correspondence should be addressed. Tel: +33 1 47 40 77 68; Email: aat{at}mrc-lmb.cam.ac.uk
Received March 9, 2009. Revised June 4, 2009. Accepted June 22, 2009.
In vivo nucleosomes often occupy well-defined preferred positions on genomic DNA. An important question is to what extent these preferred positions are directly encoded by the DNA sequence itself. We derive here from in vivo positions, accurately mapped by partial micrococcal nuclease digestion, a translational positioning signal that identifies the approximate midpoint of DNA bound by a histone octamer. This midpoint is, on average, highly A/T rich (
73%) and, in particular, the dinucleotide TpA occurs preferentially at this and other outward-facing minor grooves. We conclude that in this set of sequences the sequence code for DNA bending and nucleosome positioning differs from the other described sets and we suggest that the enrichment of AT-containing dinucleotides at the centre is required for local untwisting. We show that this signature is preferentially associated with nucleosomes flanking promoter regions and suggest that it contributes to the establishment of gene-specific nucleosome arrays.