The actin-MRTF-SRF transcriptional circuit controls tubulin acetylation via α-TAT1 gene expression.
Jaime Fernández-BarreraMiguel Bernabé-RubioJavier Casares-AriasLaura RangelLaura Fernández-MartínIsabel CorreasMiguel A AlonsoPublished in: The Journal of cell biology (2018)
The role of formins in microtubules is not well understood. In this study, we have investigated the mechanism by which INF2, a formin mutated in degenerative renal and neurological hereditary disorders, controls microtubule acetylation. We found that silencing of INF2 in epithelial RPE-1 cells produced a dramatic drop in tubulin acetylation, increased the G-actin/F-actin ratio, and impaired myocardin-related transcription factor (MRTF)/serum response factor (SRF)-dependent transcription, which is known to be repressed by increased levels of G-actin. The effect on tubulin acetylation was caused by the almost complete absence of α-tubulin acetyltransferase 1 (α-TAT1) messenger RNA (mRNA). Activation of the MRTF-SRF transcriptional complex restored α-TAT1 mRNA levels and tubulin acetylation. Several functional MRTF-SRF-responsive elements were consistently identified in the α-TAT1 gene. The effect of INF2 silencing on microtubule acetylation was also observed in epithelial ECV304 cells, but not in Jurkat T cells. Therefore, the actin-MRTF-SRF circuit controls α-TAT1 transcription. INF2 regulates the circuit, and hence microtubule acetylation, in cell types where it has a prominent role in actin polymerization.
Keyphrases
- transcription factor
- gene expression
- histone deacetylase
- cell migration
- induced apoptosis
- cell cycle arrest
- stem cells
- dna methylation
- single cell
- genome wide
- mesenchymal stem cells
- cell proliferation
- cell therapy
- endoplasmic reticulum stress
- genome wide identification
- binding protein
- cancer therapy
- subarachnoid hemorrhage
- drug delivery
- drug induced