Nucleic Acids Research Advance Access originally published online on December 5, 2008
Nucleic Acids Research 2009 37(2):533-549; doi:10.1093/nar/gkn948
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Nucleic Acids Research, 2009, Vol. 37, No. 2 533-549
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Computational Biology |
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation
1University of Padova, Department of Biology, Via G. Colombo 3, 35121, Padova and 2University of Modena and Reggio Emilia, Department of Biomedical Sciences, via Campi 287, 41100, Modena, Italy
*To whom correspondence should be addressed. Tel: +39 49 827 6502; Fax: +39 49 827 6209; Email: stefibo{at}bio.unipd.it
Received October 15, 2008. Revised November 7, 2008. Accepted November 7, 2008.
Genes co-expressed may be under similar promoter-based and/or position-based regulation. Although data on expression, position and function of human genes are available, their true integration still represents a challenge for computational biology, hampering the identification of regulatory mechanisms. We carried out an integrative analysis of genomic position, functional annotation and promoters of genes expressed in myeloid cells. Promoter analysis was conducted by a novel multi-step method for discovering putative regulatory elements, i.e. over-represented motifs, in a selected set of promoters, as compared with a background model. The combination of transcriptional, structural and functional data allowed the identification of sets of promoters pertaining to groups of genes co-expressed and co-localized in regions of the human genome. The application of motif discovery to 26 groups of genes co-expressed in myeloid cells differentiation and co-localized in the genome showed that there are more over-represented motifs in promoters of co-expressed and co-localized genes than in promoters of simply co-expressed genes (CEG). Motifs, which are similar to the binding sequences of known transcription factors, non-uniformly distributed along promoter sequences and/or occurring in highly co-expressed subset of genes were identified. Co-expressed and co-localized gene sets were grouped in two co-expressed genomic meta-regions, putatively representing functional domains of a high-level expression regulation.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.