Función de las proteínas Polycomb/Trithorax y Dp53 en la regulación de la expresión génica de Drosophila
- Autores: Rocío Simón Scristán
- Directores de la Tesis: Ana de Busturia y Jimeno (dir. tes.)
- Lectura: En la Universidad Autónoma de Madrid ( España ) en 2013
- Idioma: español
- Tribunal Calificador de la Tesis: José Fernández Piqueras (presid.), María Inmaculada González García (secret.), Margarita Sánchez Beato Gómez (voc.), Carmela Cales Bourdet (voc.), Miguel Ángel Vidal Caballero (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: Biblos-e Archivo
- Resumen
Key words: Drosophila, epigenetic, proliferation, apoptosis, Polycomb, Trithorax, dRYBP, Dp53.
SUMMARY The mechanisms controlling cellular proliferation and apoptosis are essential to animal development and survival. The Polycomb (PcG) and trithorax (trxG) groups of proteins are epigenetic regulators that play a pivotal role in the regulation of the balance between these two processes. They function by ensuring the maintenance of the repressed or activated gene transcriptional states during cellular proliferation. Moreover, the p53 pathway is also instrumental in the control of the homeostatic balance between proliferation and apoptosis. In this Thesis, I have studied the effects on apoptosis and proliferation that the modulation of the levels of expression of the PcG/trxG proteins have in the development of wing imaginal discs in Drosophila. Furthermore, I have analyzed the mechanisms by which Dp53 induces both apoptosis and proliferation. Finally I have also studied the dRYBP interacting proteins by mass spectrometry and analyzed its function together with dKDM2, SCE/dRING and dBRE1 in the regulation of homeotic gene expression.
The conclusions of this Thesis work are the following: 1) The modulation of the levels of expression of the PcG/trxG proteins affects the proliferation and apoptosis of the wing imaginal discs. Proteins that belong to the same protein complex have different outcomes on these processes. 2) High levels of Polyhomeotic protein induce hyperplastic overgrowths through the activation of the JAK/STAT pathway and Wingless, dMyc and Decapentaplegic factors, accompanied by a strong induction of apoptosis and weak changes in cellular identities. 3) Low levels of Polyhomeotic protein induce neoplastic overgrowths through the activation of the JAK/STAT pathway and Wingless and Decapentaplegic factors, accompanied by a weak induction of apoptosis and strong changes in cellular identities. 4) Both, high and low levels of expression of dRYBP induce apoptosis in a Dp53-dependent way. 5) Dp53 gene interacts genetically with Notch and wingless genes. 6) Dp53 protein regulates Notch expression transcriptionally, whose promoter contains Dp53 binding sites. 7) High levels of Dp53 produce, besides apoptosis, proliferation in the wing imaginal disc. This proliferation, which could be independent of apoptosis, requires the activation of Notch and Wingless expression. 8) The study of dRYBP-interacting proteins by mass spectrometry indicates that dRYBP interacts with a high variety of proteins, including proteins of the Polycomb and trithorax group and proteins involved in the ubiquitination process. 9) dRYBP interacts genetically with Sce/dRing, dkdm2 and dBre1. Moreover, the dRYBP, SCE/dRING, dKDM2 and dBRE1 proteins interact molecularly. Furthermore, dRYBP together with SCE/dRING and dKDM2 participates in the maintenance of transcriptional silencing mediated by the MCP element, a Polycomb Response Element (PRE), of the Abdominal-B gene. 10) dRYBP, SCE/dRING, dKDM2 and dBRE1 are involved in the maintenance of homeotic gene expression to promote intermediated states of transcriptional repression and activation.
