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Open Access Research article

Comparative genomics using teleost fish helps to systematically identify target gene bodies of functionally defined human enhancers

Nazia Parveen1, Ayesha Masood1, Nouman Iftikhar1, Bushra F Minhas1, Rashid Minhas1, Uzma Nawaz2 and Amir Ali Abbasi1*

Author Affiliations

1 National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan

2 Department of Statistics, Govt: Post Graduate College For Women, Kutchary Road, Multan 60000, Pakistan

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BMC Genomics 2013, 14:122  doi:10.1186/1471-2164-14-122

Published: 23 February 2013

Abstract

Background

Human genome is enriched with thousands of conserved non-coding elements (CNEs). Recently, a medium throughput strategy was employed to analyze the ability of human CNEs to drive tissue specific expression during mouse embryogenesis. These data led to the establishment of publicly available genome wide catalog of functionally defined human enhancers. Scattering of enhancers over larger regions in vertebrate genomes seriously impede attempts to pinpoint their precise target genes. Such associations are prerequisite to explore the significance of this in vivo characterized catalog of human enhancers in development, disease and evolution.

Results

This study is an attempt to systematically identify the target gene-bodies for functionally defined human CNE-enhancers. For the purpose we adopted the orthology/paralogy mapping approach and compared the CNE induced reporter expression with reported endogenous expression pattern of neighboring genes. This procedure pinpointed specific target gene-bodies for the total of 192 human CNE-enhancers. This enables us to gauge the maximum genomic search space for enhancer hunting: 4 Mb of genomic sequence around the gene of interest (2 Mb on either side). Furthermore, we used human-rodent comparison for a set of 159 orthologous enhancer pairs to infer that the central nervous system (CNS) specific gene expression is closely associated with the cooperative interaction among at least eight distinct transcription factors: SOX5, HFH, SOX17, HNF3β, c-FOS, Tal1beta-E47S, MEF and FREAC.

Conclusions

In conclusion, the systematic wiring of cis-acting sites and their target gene bodies is an important step to unravel the role of in vivo characterized catalog of human enhancers in development, physiology and medicine.

Keywords:
CNEs; Human genome; Enhancers; Teleost fish; Synteny; Central nervous system; Transcriptional factors