hnulp1, a basic helix-loop-helix protein with a novel transcriptional repressive domain, inhibits transcriptional activity of serum response factor.
Many bHLH proteins are involved in cardiac development and cardiovascular diseases. Herein, we identified and characterized the human homologue (hnulp1) of mouse gene nulp1. The predicted protein contains a bHLH domain and a DUF654 domain in N-terminal and C-terminal, respectively. Northern blot analysis shows that a 2.3-kb transcript expressed broadly in early human embryonic and adult tissues, especially with a higher level in adult heart. hnulp1 is a transcription repressor when fused to GAL4 DNA-binding domain and co-transfected with VP-16, in which DUF654 motif represents the basal transcriptional repressive activity. Treatment of cells with trichostatin A can relieve this repression, suggesting that the DUF654 motif acts through increasing deacetylase activity at the GAL4-driven promoter. Overexpression of hnulp1 protein in COS-7 cells inhibits the transcriptional activity of serum response factor (SRF), suggesting that hnulp1 may act as a novel bHLH transcriptional repressor in SRF signaling pathway to mediate cellular functions.
Cai
Zhenyu
Z
The Center for Heart Development, College of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, PR China.
Wang
Yuequn
Y
Yu
Weishi
W
Xiao
Jing
J
Li
Yongqing
Y
Liu
Lian
L
Zhu
Chuanbing
C
Tan
Kunrong
K
Deng
Yun
Y
Yuan
Wuzhou
W
Liu
Mingyao
M
Wu
Xiushan
X
D000595:Amino Acid Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000737:chemistry; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004622:Embryo, Mammalian / Q000378:metabolism; D019143:Evolution, Molecular; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D026362:Serum Response Factor / Q000037:antagonists & inhibitors*; D015533:Transcriptional Activation
D051792:Basic Helix-Loop-Helix Proteins; D006655:Histone Deacetylases; D012097:Repressor Proteins; D026362:Serum Response Factor; C510400:TCF25 protein, human