Tcf7l2-Tcf4 Transcriptional Repressor Function Requires HDAC Activity in the Developing Vertebrate CNSReportar como inadecuado




Tcf7l2-Tcf4 Transcriptional Repressor Function Requires HDAC Activity in the Developing Vertebrate CNS - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

The generation of functionally distinct neuronal subtypes within the vertebrate central nervous system CNS requires the precise regulation of progenitor gene expression in specific neuronal territories during early embryogenesis. Accumulating evidence has implicated histone deacetylase HDAC proteins in cell specification, proliferation, and differentiation in diverse embryonic and adult tissues. However, although HDAC proteins have shown to be expressed in the developing vertebrate neural tube, their specific role in CNS neural progenitor fate specification remains unclear. Prior work from our lab showed that the Tcf7l2-Tcf4 transcription factor plays a key role in ventral progenitor lineage segregation by differential repression of two key specification factors, Nkx2.2 and Olig2. In this study, we found that administration of HDAC inhibitors Valproic Acid VPA, Trichostatin-A TSA, or sodium butyrate in chick embryos in ovo disrupted normal progenitor gene segregation in the developing neural tube, indicating that HDAC activity is required for this process. Further, using functional and pharmacological approaches in vivo, we found that HDAC activity is required for the differential repression of Nkx2.2 and Olig2 by Tcf7l2-Tcf4. Finally, using dominant-negative functional assays, we provide evidence that Tcf7l2-Tcf4 repression also requires Gro-TLE-Grg co-repressor factors. Together, our data support a model where the transcriptional repressor activity of Tcf7l2-Tcf4 involves functional interactions with both HDAC and Gro-TLE-Grg co-factors at specific target gene regulatory elements in the developing neural tube, and that this activity is required for the proper segregation of the Nkx2.2 p3 and Olig2 pMN expressing cells from a common progenitor pool.



Autor: Hui Wang, Michael P. Matise

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados