Human heart LIM protein activates atrial-natriuretic-factor gene expression by interacting with the cardiac-restricted transcription factor Nkx2.5.
hhLIM [human heart LIM (Lin-11/IsI-1/Mec-3) protein] is a muscle-specific LIM-only protein that consists of two LIM motifs. hhLIM functions as a positive regulator for cardiac hypertrophy. Here we report that hhLIM serves as a cofactor regulating the expression of the ANF (atrial natriuretic factor) gene in H9c2 rat cardiomyoblast cells. We found that hhLIM promoted the expression of the ANF gene in H9c2 cells, but not in A293 human embryonic kidney cells. Furthermore, we showed that hhLIM interacted with Nkx2.5 (a cardiac-restricted transcription factor) in vivo and in vitro using its N-terminal LIM domain and enhanced the binding ability of Nkx2.5 to the NKE (Nkx2.5-binding element) boxes in the ANF promoter. These results suggest that hhLIM promotes the specific expression of the ANF gene by co-operating with Nkx2.5.
Zheng
Bin
B
Hebei Laboratory of Medical Biotechnology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, People's Republic of China.
Han
Mei
M
Wen
Jin-Kun
JK
Zhang
Rui
R
D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D060588:LIM Domain Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D060588:LIM Domain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors; C090114:cysteine and glycine-rich protein 3; D009320:Atrial Natriuretic Factor