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

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 neur...

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Autores principales: Liu, Rui, Hannenhalli, Sridhar, Bucan, Maja
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728526/
https://www.ncbi.nlm.nih.gov/pubmed/19570198
http://dx.doi.org/10.1186/gb-2009-10-7-r72
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author Liu, Rui
Hannenhalli, Sridhar
Bucan, Maja
author_facet Liu, Rui
Hannenhalli, Sridhar
Bucan, Maja
author_sort Liu, Rui
collection PubMed
description 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.
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spelling pubmed-27285262009-08-18 Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons Liu, Rui Hannenhalli, Sridhar Bucan, Maja Genome Biol Research 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. BioMed Central 2009 2009-07-01 /pmc/articles/PMC2728526/ /pubmed/19570198 http://dx.doi.org/10.1186/gb-2009-10-7-r72 Text en Copyright © 2009 Liu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Liu, Rui
Hannenhalli, Sridhar
Bucan, Maja
Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons
title Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons
title_full Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons
title_fullStr Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons
title_full_unstemmed Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons
title_short Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons
title_sort motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728526/
https://www.ncbi.nlm.nih.gov/pubmed/19570198
http://dx.doi.org/10.1186/gb-2009-10-7-r72
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