The gene encoding the mouse contactin-1 axonal glycoprotein is regulated by the collier/Olf1/EBF family early B-Cell factor 2 transcription factor

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Abstract

The Contactin-1 axonal glycoprotein (formerly F3/Contactin) plays a relevant role in cerebellar ontogenesis, as shown in Contactin-1 KO-mice and in transgenic mice misexpressing the corresponding cDNA from a heterologous promoter. Likewise, null mutant mice for the Collier/Olf1/Early B-cell family transcription factor EBF2, in which Purkinje neuron development is primarily affected, exhibit abnormalities in cerebellar corticogenesis. Here, to evaluate the contribution to theEbf2null phenotype of changes in the profile of Contactin-1, we study its expression inEbf2null mice. In addition, we explore the activation profile of theCntn1gene promoter upon transferring theEbf2mutation to transgenic mice expressing an enhanced green fluorescent protein reporter under control ofCntn1gene regulatory sequences. InEbf2null mice, Contactin-1 protein expression andCntn1gene promoter activity are both downregulated during embryonic and early postnatal cerebellar development, both in the rostral and caudal folia, while in the latter an upregulation is observed at postnatal day 8.In vitro, vectors driving EBF1,2,3 transcription factors from a cytomegalovirus (CMV) promoter transactivate aCntn1-Choline acetyltransferse (CAT) promoter-reporter construct in cotransfection assays and, accordingly, by chromatin immunoprecipitation, we show that theCntn1gene 5′ flanking region is bound by the EBF2 transcription factor, consistent with the evidence that this region bears the cognate deoxyribonucleic acid (DNA) consensus sequences. These data indicate that Contactin-1 expression is dependent upon EBF factors, suggesting that theCntn1gene belongs to the expanding regulatory cascade driven by these transcriptional regulators so that changes in its activation may contribute to the phenotype ofEbf2null mutant mice. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1420–1440, 2015

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