Naturally Occurring Nucleosome Positioning Signals in Human Exons
and Introns
Pierre Baldi, Søren Brunak, Yves Chauvin, Anders Krogh
Journal of Molecular Biology , 263(4):503-510 (Nov 8, 1996)
Abstract
We describe the structural implications of a periodic pattern found in human exons and introns by hidden
Markov models. We show that exons (besides the reading frame) have a specific sequential structure in
the form of a pattern with triplet consensus non-T(A/T)G, and a minimal periodicity of roughly ten
nucleotides. The periodic pattern is also present in intron sequences, although the strength per nucleotide
is weaker. Using two independent profile methods based on triplet bendability parameters from DNase I
experiments and nucleosome positioning data, we show that the pattern in multiple alignments of
internal exon and intron sequences corresponds to a periodic "in phase" bending potential towards the
major groove of the DNA. The nucleosome positioning data show that the consensus triplets (and their
complements) have a preference for locations on a bent double helix where the major groove faces inward
and is compressed. The in-phase triplets are located adjacent to GCC/GGC triplets known to have the
strongest bias in their positioning on the nuclesome. Analysis of mRNA sequences encoding proteins
with known tertiary structure exclude the possibility that the pattern is a consequence of the previously
well-known periodicity caused by the encoding of alpha-helices in proteins. Finally, we discuss the
relation between the bending potential of coding and non-coding regions and its impact on the
translational positioning of nucleosomes and the recognition of genes by the transcriptional machinery.
