Differential Binding of Creb, Usf, and c-myc to the Calreticulin Human Specific –220c May Be Linked with the Evolution of Higher Brain Functions in Human

Abstract

Introduction

We have previously reported a human-specific nucleotide in the promoter sequence of the calreticulin (CALR) gene at position –220C, which is the site of action of valproic acid.

Objectives

Reversion of this nucleotide to the ancestral type, –220A, co-occurs with severe deficit in higher brain cognitive functions.

Aims

In the current study, we compare the pattern of protein binding between –220C and –220A.

Methods

Antibodies reactive against transcription factors CREB, USF, and c-Myc were used to identify the specific proteins involved in complexes with DNA using electrophoretic mobility shift assay (EMSA).

Results

Significant increase was observed in the overall protein complexes binding to the –220 C allele vs. –220A. The transcription factors, CREB, USF, and c-Myc, were differentially bound to –220C, represented by supershifts.

Conclusions

We propose that differential binding of CREB, USF, and c-Myc to CALR nucleotide –220C may be linked with the evolution of higher brain functions in human.

Disclosure of interest

The author has not supplied his/her declaration of competing interest.