A novel zinc finger protein Zfp637 behaves as a repressive regulator in myogenic cellular differentiation

Abstract

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.

IL-6 mediates differentiation disorder during spermatogenesis in obesity-associated inflammation by affecting the expression of Zfp637 through the SOCS3/STAT3 pathway

“…In addition, tissue-specific expression of Zfp637 has been correlated with telomerase activity1, and thus, it may be involved in multiple biological behaviors. In our previous studies, we confirmed that Zfp637 could repress myogenic cellular differentiation2, but the specific functions of Zfp637 in germ cell differentiation remain unknown. In this study, we examined the expression of Zfp637 in mouse spermatogonia and then evaluated the effects of Zfp637 overexpression or underexpression on germ cell differentiation.…”

“…According to a bioinformatics analysis, the zinc finger transcription factor protein Zfp637 may play a role in gene regulation, thus impacting the biological behavior of cells. Our previous study has also confirmed that Zfp637 plays an important role in the differentiation of cells2. Consequently, immunocytochemistry (ICC) was performed to detect the expression of Zfp637 in mouse spermatogonial GC-1 spg cells.…”

Zinc finger protein 637 protects cells against oxidative stress-induced premature senescence by mTERT-mediated telomerase activity and telomere maintenance

“…51 In a previous report, we hypothesized that Zfp637 may directly regulate mTERT by interacting with the core promoter region or indirectly promote mTERT transcription by regulating or synergistically cooperating with Sp1 and Sp3. 24 In this study, we demonstrated that Zfp637 binds to the mTERT promoter (−535/−502) specifically and activates the transcription of mTERT directly. However, the sequence of the Zfp637-binding site has not yet been elucidated and further experiments are needed to explore the Zfp637-responsive elements.…”

“…41 Our previous investigation demonstrated that Zfp637 promotes myogenic cellular proliferation and inhibits cellular differentiation by upregulating mTERT. 24 However, the mechanism underlying the regulation of mTERT by Zfp637 has not been previously elucidated. In this study, we focused on the relationship between Zfp637 and mTERT in the model of oxidative stress-induced premature senescence.…”

“…We have reported that Zfp637 is located in nucleus and behaves as a repression regulator in myogenic cellular differentiation by promoting mTERT expression. 24 Based on its structural characterization and location, we predict that Zfp637 likely acts as a DNA-binding protein to regulate gene transcription. An analysis of Zfp637 in the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) indicates that Zfp637 may have a potential role in oxidative stress, 25, 26, 27 and our previous study proved that Zfp637 expression was significantly altered in NIH3T3 cells treated with 200  μ M H 2 O 2 in a time-dependent manner.…”