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Protein-Protein Interaction Among the FoxP Family Members and their Regulation of Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System

The Forkhead transcription factor FOXP2 is implicated in speech perception and production. The avian homolog, FoxP2 contributes to song learning and production in birds. In human cell lines, transcriptional activity of FOXP2 requires homo-dimerization or dimerization with paralogs FOXP1 or FOXP4. Wh...

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Autores principales: Mendoza, Ezequiel, Scharff, Constance
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410569/
https://www.ncbi.nlm.nih.gov/pubmed/28507505
http://dx.doi.org/10.3389/fnmol.2017.00112
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author Mendoza, Ezequiel
Scharff, Constance
author_facet Mendoza, Ezequiel
Scharff, Constance
author_sort Mendoza, Ezequiel
collection PubMed
description The Forkhead transcription factor FOXP2 is implicated in speech perception and production. The avian homolog, FoxP2 contributes to song learning and production in birds. In human cell lines, transcriptional activity of FOXP2 requires homo-dimerization or dimerization with paralogs FOXP1 or FOXP4. Whether FoxP dimerization occurs in the brain is unknown. We recently showed that FoxP1, FoxP2 and FoxP4 (FoxP1/2/4) proteins are co-expressed in neurons of Area X, a song control region in zebra finches. We now report on dimer- and oligomerization of zebra finch FoxPs and how this affects transcription. In cell lines and in the brain we identify homo- and hetero-dimers, and an oligomer composed of FoxP1/2/4. We further show that FoxP1/2 but not FoxP4 bind to the regulatory region of the target gene Contactin-associated protein-like 2 (CNTNAP2). In addition, we demonstrate that FoxP1/4 bind to the regulatory region of very low density lipoprotein receptor (VLDLR), as has been shown for FoxP2 previously. Interestingly, FoxP1/2/4 individually or in combinations regulate the promoters for SV40, zebra finch VLDLR and CNTNAP2 differentially. These data exemplify the potential for complex transcriptional regulation of FoxP1/2/4, highlighting the need for future functional studies dissecting their differential regulation in the brain.
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spelling pubmed-54105692017-05-15 Protein-Protein Interaction Among the FoxP Family Members and their Regulation of Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System Mendoza, Ezequiel Scharff, Constance Front Mol Neurosci Neuroscience The Forkhead transcription factor FOXP2 is implicated in speech perception and production. The avian homolog, FoxP2 contributes to song learning and production in birds. In human cell lines, transcriptional activity of FOXP2 requires homo-dimerization or dimerization with paralogs FOXP1 or FOXP4. Whether FoxP dimerization occurs in the brain is unknown. We recently showed that FoxP1, FoxP2 and FoxP4 (FoxP1/2/4) proteins are co-expressed in neurons of Area X, a song control region in zebra finches. We now report on dimer- and oligomerization of zebra finch FoxPs and how this affects transcription. In cell lines and in the brain we identify homo- and hetero-dimers, and an oligomer composed of FoxP1/2/4. We further show that FoxP1/2 but not FoxP4 bind to the regulatory region of the target gene Contactin-associated protein-like 2 (CNTNAP2). In addition, we demonstrate that FoxP1/4 bind to the regulatory region of very low density lipoprotein receptor (VLDLR), as has been shown for FoxP2 previously. Interestingly, FoxP1/2/4 individually or in combinations regulate the promoters for SV40, zebra finch VLDLR and CNTNAP2 differentially. These data exemplify the potential for complex transcriptional regulation of FoxP1/2/4, highlighting the need for future functional studies dissecting their differential regulation in the brain. Frontiers Media S.A. 2017-05-01 /pmc/articles/PMC5410569/ /pubmed/28507505 http://dx.doi.org/10.3389/fnmol.2017.00112 Text en Copyright © 2017 Mendoza and Scharff. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Mendoza, Ezequiel
Scharff, Constance
Protein-Protein Interaction Among the FoxP Family Members and their Regulation of Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System
title Protein-Protein Interaction Among the FoxP Family Members and their Regulation of Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System
title_full Protein-Protein Interaction Among the FoxP Family Members and their Regulation of Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System
title_fullStr Protein-Protein Interaction Among the FoxP Family Members and their Regulation of Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System
title_full_unstemmed Protein-Protein Interaction Among the FoxP Family Members and their Regulation of Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System
title_short Protein-Protein Interaction Among the FoxP Family Members and their Regulation of Two Target Genes, VLDLR and CNTNAP2 in the Zebra Finch Song System
title_sort protein-protein interaction among the foxp family members and their regulation of two target genes, vldlr and cntnap2 in the zebra finch song system
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410569/
https://www.ncbi.nlm.nih.gov/pubmed/28507505
http://dx.doi.org/10.3389/fnmol.2017.00112
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