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Background  Along with sodium/calcium (Ca 2+ ) exchangers, plasma membrane Ca 2+  ATPases (ATP2Bs) are main regulators of intracellular Ca 2+  levels. There are four ATP2B paralogs encoded by four different genes.  Atp2b2  encodes the protein pump with the fastest activation, ATP2B2. In mice, the  Atp2b2  transcript has several alternate transcriptional start site variants:  α ,  β ,  µ  and  δ . These variants are expressed in developmental and tissue specific manners. The  α  and  β Atp2b2  transcripts are equally expressed in the brain.  αAtp2b2  is the only transcript found in the outer hair cells of young mice (Silverstein RS, Tempel BL. in Neuroscience 141:245–257,  2006 ). Mutations in the coding region of the mouse  Atp2b2  gene indicate a narrow window for tolerated dysfunction of the ATP2B2 protein, specifically in the auditory system. This highlights the necessity of tight regulation of this gene for normal cell physiology.    Results  Although ATP2Bs are important regulators of Ca 2+  in many cell types, little is known about their transcriptional regulation. This study identifies the proximal promoter of the  αAtp2b2  transcript. Further investigations indicate that ATOH1 and EGR1 modulate promoter activity. Additionally, we report that EGR1 increases endogenous expression of  Atp2b2  transcript in two cell lines. Electrophoretic mobility shift assays (EMSA) indicate that EGR1 binds to a specific site in the CpG island of the  αAtp2b2  promoter.    Conclusion  This study furthers our understanding of  Atp2b2  regulation by: (I) elucidating transcriptional regulatory mechanisms for  Atp2b2,  and (II) identifying transcription factors that modulate expression of  Atp2b2  in the brain and peripheral auditory system and (III) allows for future studies modulating gene expression of  Atp2b2.Electronic supplementary material  The online version of this article (doi:10.1186/s12867-017-0092-1) contains supplementary material, which is available to authorized users.

bmc molecular biology

Early growth response protein 1 regulates promoter activity of α-plasma membrane calcium ATPase 2, a major calcium pump in the brain and auditory system