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

Frontiers in Molecular Neuroscience
Ezequiel Mendoza, Constance Scharff

Abstract

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...Continue Reading

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Citations

Jan 31, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Marissa CoGenevieve Konopka
Feb 11, 2020·The Journal of Comparative Neurology·Peter V LovellClaudio V Mello
Mar 20, 2019·Angewandte Chemie·Katharina HäußermannHendrik Dietz
Jul 15, 2021·EMBO Reports·Joery den HoedSimon E Fisher

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Datasets Mentioned

BETA
KX943238

Methods Mentioned

BETA
CoIP
Co-IP
X-ray
Dissection
transfection
ELISA
PCR
electrophoretic mobility shift
co-immunoprecipitation
co-immunoprecipitations

Software Mentioned

GraphPad Prism
CpG plot
R
GraphPad
R Core

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