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deltaEF1 repressor controls selectively p53 family members during differentiation
Giulia Fontemaggi1, Aymone Gurtner, Alexander Damalas
1Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy.
Oncogene
|July 12, 2005
Summary
The p53 family, including p73 and p63, regulates cell growth and development. Muscle regulatory factors and deltaEF1 control p73 gene expression, impacting muscle and skin cell differentiation.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- The p53 family of transcription factors (p53, p73, p63) is crucial for cell growth suppression, apoptosis, differentiation, and development.
- While p53 deficiency leads to tumors, p73 and p63 deficiencies cause severe developmental defects.
Purpose of the Study:
- To investigate the transcriptional regulation of the p73 gene by muscle regulatory factors and the role of deltaEF1 in this process.
- To explore the function of deltaEF1 in the transcriptional regulation of p53 family members during keratinocytic differentiation.
Main Methods:
- Demonstration of p73 as an in vivo transcriptional target of MyoD, myogenin, Myf5, and Myf6.
- Analysis of the effect of deltaEF1/ZEB/zfhx1a on MyoD/Myf5- or MyoD/Myf6-mediated p73 activation.
- Investigation of in vivo recruitment patterns of muscle regulatory factors and deltaEF1 on p73 regulatory regions in proliferating and differentiating muscle cells.
- Examination of deltaEF1's role in p53 family member regulation during keratinocytic differentiation using mouse embryo fibroblasts and tissues from deltaEF1-deficient mice.
Main Results:
- The p73 gene is an in vivo transcriptional target of key muscle regulatory factors.
- Ectopic expression of deltaEF1 represses the transcriptional activation of p73 mediated by MyoD/Myf5 or MyoD/Myf6.
- Distinct recruitment patterns of muscle regulatory factors and deltaEF1 were observed on p73 regulatory regions in proliferating versus differentiating muscle cells.
- deltaEF1 plays a role in regulating p53 family members during keratinocytic differentiation, with deltaEF1-deficient fibroblasts showing unbalanced expression of DeltaNp63, TAp73, and DeltaNp73.
- Analysis of deltaEF1+/- mouse tissues revealed selective enrichment of DeltaNp63 in the skin.
Conclusions:
- Muscle regulatory factors and deltaEF1 are key regulators of p73 gene expression during muscle cell differentiation.
- deltaEF1 is involved in the transcriptional control of p53 family members, particularly influencing DeltaNp63 expression in skin development.