Mecanismos epigenéticos en la diferenciación eritroide y linfoideel regulador transcripcional CTCF y fármacos epigenéticos

  1. GARCIA GAIPO, LORENA
Supervised by:
  1. Javier León Serrano Director
  2. María Dolores Delgado Villar Co-director

Defence university: Universidad de Cantabria

Fecha de defensa: 13 December 2019

Committee:
  1. José Carlos Díez Ballesteros Chair
  2. Flor María Pérez Campo Secretary
  3. Veronica Torrano Moya Committee member

Type: Thesis

Teseo: 607237 DIALNET lock_openUCrea editor

Abstract

CTCF transcription factor can interact with a high number of DNA sequences and is involved in the regulation of gene transcription, chromatin insulation, epigenetic regulation and genome organization. Previous results of our group indicated a possible role of CTCF in the regulation of erythroid differentiation. Our results indicate that CTCF downregulation inhibits erythropoiesis through the regulation of erythroid specific genes in human hematopoietic cells. In contrast to genetic alterations, epigenetic modifications are potentially reversible and can be targeted with specific epigenetic drugs. Therapy with epigenetic drugs has an enormous potential in lymphoma-8 treatment. Combination treatment with romidepsin (HDAC inhibitor) and JQ1 (BET bromodomain inhibitor) synergistically induces apoptosis, cell cycle arrest and plasma cell differentiation. These results suggest a potential role for the treatment of aggressive 8-cell lymphomas.