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Genome Biol. 2009;10(7):R72. doi: 10.1186/gb-2009-10-7-r72. Epub 2009 Jul 1.

Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons.

Author information

  • 1Department of Genetics and Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

BACKGROUND:

Hundreds of proteins modulate neurotransmitter release and synaptic plasticity during neuronal development and in response to synaptic activity. The expression of genes in the pre- and post-synaptic neurons is under stringent spatio-temporal control, but the mechanism underlying the neuronal expression of these genes remains largely unknown.

RESULTS:

Using unbiased in vivo and in vitro screens, we characterized the cis elements regulating the Rab3A gene, which is expressed abundantly in presynaptic neurons. A set of identified regulatory elements of the Rab3A gene corresponded to the defined Rab3A multi-species conserved elements. In order to identify clusters of enriched transcription factor binding sites, for example, cis-regulatory modules, we analyzed intergenic multi-species conserved elements in the vicinity of nine presynaptic genes, including Rab3A, that are highly and specifically expressed in brain regions. Sixteen transcription factor binding motifs were over-represented in these multi-species conserved elements. Based on a combined occurrence for these enriched motifs, multi-species conserved elements in the vicinity of 107 previously identified presynaptic genes were scored and ranked. We then experimentally validated the scoring strategy by showing that 12 of 16 (75%) high-scoring multi-species conserved elements functioned as neuronal enhancers in a cell-based assay.

CONCLUSIONS:

This work introduces an integrative strategy of comparative genomics, experimental, and computational approaches to reveal aspects of a regulatory network controlling neuronal-specific expression of genes in presynaptic neurons.

PMID:
19570198
[PubMed - indexed for MEDLINE]
PMCID:
PMC2728526
Free PMC Article

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