Open Access Highly Accessed Research article

CpG islands under selective pressure are enriched with H3K4me3, H3K27ac and H3K36me3 histone modifications

Most Mauluda Akhtar14*, Giovanni Scala123, Sergio Cocozza14, Gennaro Miele123 and Antonella Monticelli15

Author Affiliations

1 “Gruppo Interdipartimentale di Bioinformatica e Biologia Computazionale, Università di Napoli “Federico II” - Università di Salerno, Naples, Italy

2 Dipartimento di Fisica, Università degli Studi di Napoli “Federico II”, Naples, Italy

3 Istituto Nazionale di Fisica Nucleare – Sezione di Napoli, Naples, Italy

4 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli “Federico II”, Naples, Italy

5 CNR, Istituto di Endocrinologia ed Oncologia Sperimentale IEOS, Naples, Italy

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BMC Evolutionary Biology 2013, 13:145  doi:10.1186/1471-2148-13-145

Published: 10 July 2013



Histone modification is an epigenetic mechanism that influences gene regulation in eukaryotes. In particular, histone modifications in CpG islands (CGIs) are associated with different chromatin states and with transcription activity. Changes in gene expression play a crucial role in adaptation and evolution.


In this paper, we have studied, using a computational biology approach, the relationship between histone modifications in CGIs and selective pressure in Homo sapiens. We considered three histone modifications: histone H3 lysine 4 trimethylation (H3K4me3), histone H3 lysine 27 acetylation (H3K27ac) and histone H3 lysine 36 trimethylation (H3K36me3), and we used the publicly available genomic-scale histone modification data of thirteen human cell lines. To define regions under selective pressure, we used three distinct signatures that mark selective events from different evolutionary periods. We found that CGIs under selective pressure showed significant enrichments for histone modifications.


Our result suggests that, CGIs that have undergone selective events are characterized by epigenetic signatures, in particular, histone modifications that are distinct from CGIs with no evidence of selection.

Epigenetic; Selective pressure; CpG islands; H3K4me3; H3K27ac; H3K36me3