In the past studies

it is shown that cardiac troponin I (cTnI

encoded by

TNNI3

)

as a cytoplasmic protein

is an inhibitory subunit in troponin complex

and involves in cardiomyocyte diastolic regulation. Here

we assessed a novel role of cTnI as a nucleoprotein. Firstly

the nuclear translocation of cTnI was found in mouse

human fetuses and rat heart tissues. In addition

there were differences in percentage of intranuclear cTnI in different conditions. Based on weighted gene co-expression network analyses (WGCNA) and verification in cell experiments

a strong expression correlation was found between

TNNI3

and

Atp2a2

which encodes sarco-endoplasmic reticulum Ca

2+

ATPase isoform 2a (SERCA2a)

and involves in ATP hydrolysis and Ca

2+

transient. TNNI3 gain and loss caused Atpa2a2 increase/decrease in a dose-dependent manner both in mRNA and protein levels

in vivo

and

in vitro

. By using ChIP-sequence we demonstrated specific binding DNA sequences of cTnI were enriched in

ATP2a2

promoter −239∼–889 region and the specific binding sequence motif of cTnI was analyzed by software as "CCAT"

which has been reported to be required for

YY1

binding to the promoter region of

YY1

-related genes. Moreover

it was further verified that pcDNA3.1 (−)-TNNI3 could express cTnI proteins and increase the promoter activity of

Atp2a2

through luciferase report assay. In the end

we evaluated beat frequencies

total ATP contents

Ca

2+

transients in

TNNI3

-siRNA myocardial cells. These findings indicated

for the first time

cTnI may regulate

Atp2a2

in cardiomyocytes as a co-regulatory factor and participate in the regulation of intracellular Ca ions.