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

BMC Molecular Biology
Rebecca R MinichBruce L Tempel

Abstract

Along with sodium/calcium (Ca2+) exchangers, plasma membrane Ca2+ ATPases (ATP2Bs) are main regulators of intracellular Ca2+ 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. Although ATP2Bs are important regulators of Ca2+ 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 express...Continue Reading

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Citations

Oct 21, 2020·Genes·Madiha KhalidGhazala Kaukab Raja

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Methods Mentioned

BETA
PCR
transfection
transfections
RNA-Seq

Software Mentioned

Motifmap
MatInspector
UCSC genome browser
Ensembl
TFBIND

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