A novel zinc finger protein Zfp637 behaves as a repressive regulator in myogenic cellular differentiation.
Zinc finger proteins have been implicated as transcription factors in the differentiation and development of cells and tissues in higher organisms. The classical C2H2 zinc finger motif is one main type of motif of zinc finger proteins. Our previous studies have shown that Zfp637, which comprises six consecutively typical and one atypical C2H2 zinc finger motifs, is highly expressed in undifferentiated or poorly differentiated cell lines, but is moderately or slightly expressed in normal tissues. We have also demonstrated that Zfp637 can promote cell proliferation. However, its role in the regulation of cell differentiation remains unknown. We report here that endogenous Zfp637 as well as mTERT is expressed in proliferating C2C12 myoblasts and that their expression is downregulated during myogenic differentiation. Constitutive expression of Zfp637 in C2C12 myoblasts increased mTERT expression and telomerase activity, and promoted the progression of the cell cycle and cell proliferation. By contrast, endogenous repression of Zfp637 expression by RNA interference downregulated the mTERT gene and the activity of telomerase, and markedly reduced cell proliferation. Overexpression of Zfp637 also inhibited the expression of myogenic differentiation-specific genes such as MyoD and myogenin, and prevented C2C12 myoblast differentiation. Our results suggest that Zfp637 inhibits muscle differentiation through a defect in the cell cycle exit by potentially regulating mTERT expression in C2C12 myoblasts. This may provide a new research line for studying muscle differentiation.
Li
Kai
K
Division of Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, People's Republic of China.
Zhang
Jie
J
Ren
Jing-Jing
JJ
Wang
Qi
Q
Yang
Kai-Yong
KY
Xiong
Zhu-Juan
ZJ
Mao
Yong-Qiu
YQ
Qi
Yan-Yu
YY
Chen
Xiao-Wei
XW
Lan
Feng
F
Wang
Xiu-Jie
XJ
Xiao
Heng-Yi
HY
Lin
Ping
P
Wei
Yu-Quan
YQ
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; C551671:Zfp637 protein, mouse; D019098:Telomerase