Tesis doctoral de Amaya Artal Martínez De Narvajas
The histone lysine methyltransferase g9a, which generates epigenetic silencing marks, has been shown to be overexpressed in a variety of cancers including leukemia, prostate, lung and hepatocellular carcinoma. Therefore, we have studied a group of novel inhibitors, including yt-2-6, which block g9a methyltransferase activity. We analyzed the effect of g9a inhibition within various cell models. Following yt-2-6 treatment to inhibit g9a, silencing marks were abrogated from g9a target genes. Acetylases, transcription factors and rna polymerase-ii were then able to access g9a target gene promoters (including p27, lc3b, dor, and wipi1) leading to cell cycle arrest (p27-mediated) and to autophagosome formation (lc3b-, dor- and wipi1-mediated). Additionally, g9a removal from target genes (lc3b, dor and wipi1) also occurs in response to physiological autophagy-inducing stimuli, indicating a newly identified role for g9a as a central epigenetic regulator of macroautophagy. These studies have added new knowledge to the fields of epigenetics and cell biology.Q since g9a is overexpressed in various cancers, understanding the effects of g9a inhibitors is essential for its potential future use as a therapeutic target
Datos académicos de la tesis doctoral «The histone methyltransferase g9a regulates cell cycle and autophagy«
- Título de la tesis: The histone methyltransferase g9a regulates cell cycle and autophagy
- Autor: Amaya Artal Martínez De Narvajas
- Universidad: Navarra
- Fecha de lectura de la tesis: 15/11/2012
Dirección y tribunal
- Director de la tesis
- Felipe Luis Prosper Cardoso
- Tribunal
- Presidente del tribunal: María jose Calasanz abinzano
- esteban Ballestar tarin (vocal)
- sara Alvarez de andre (vocal)
- Jesús m Paramio gonzález (vocal)