Sunday, 17th December 2017

Development and Regeneration

       Epigenetic Regulation of gene expression during Drosophila development

 

 

 Busturia group 400px

 


Ana María de Busturia

CSciStaff

CPublications

 

 

 

Research Summary:

Research in my laboratory is focused on the study of the epigenetic regulation of gene ex-pression mediated by the Polycomb (PcG) and trithorax (trxG) groups of proteins as well as by microRNAs. We use Drosophila as a model system to understand normal and pathologi-cal development.

Gene transcriptional states are established as either active or repressed depending on the cellular context, biological process or developmental time. Once established, they have to be faithfully maintained throughout proliferation in order to achieve normal development. PcG and trxG proteins control the transcriptional memory and they do so by compacting chromatin and by modificationof histones. Moreover, microRNAs are also post-transcriptional regulators that bind to their mRNAs targets usually resulting in gene silencing. We aim to understand how activation and repression affects the homeostasis of an organism by studying the function of the microRNAs and the relevance of the expression levels and/or activity of the PcG/trxG proteins in normal and pathological development. This research is done through the study of the function of these epigenetic regulators in the control of cell proliferation, apoptosis and innate immune response. Moreover, to gain insight into the mechanisms that provide the PcG/trxG with the characteristics of a dynamic, reversible and adaptable control system, we also study to what external cues and signals the microRNAs and the PcG/trxG system responds.

As the microRNAs and the PcG/trxG proteins are highly conserved throughout the animal kingdom, it is expected that our research should yield results that directly impact on the understanding of the function of these proteins in other organisms, including humans. Morever, deciphering the role(s) of miRNAs and PcG/trxG may lead to a more profound understanding of the mechanisms controlling the genesis and progression of human diseases

  Figure 300px
 

 

Dp53-induced proliferation is dependent on Notch levels of expres-sion. a-f wing imaginal discs of the geno-types indicated stained with TO-PRO-3. The proliferation of the wing imaginal cells is not affected by the absence of one dose of Notch gene (b) or by the presence of an extra-dose of Notch (c) when compared to wt (a). However, the absence of one dose of Notch (e) or the presence of an extra-dose of Notch dra-matically affect the proliferation induced by high levels of Dp53 (c).

 

 

 

   
   
   

 

Relevant Publications:

  • Fereres, S., Simón, R., Mohd-Sarip, A., Verrijzer, CP., Busturia, A (2014) dRYBP counteracts chromatin-de-pendent activation and repression of transcription. PLoS One Nov 21;9(11):e113255.
  • Aparicio, R, Simoes da Silva, C., Busturia A (2014) The microRNA mir-7 contributes to the control of Drosophila wing growth. Developmental Dynamics. Jan;244(1):21-30.
  • Simón, R., Aparicio, R., Houdsen, B., Bray, S., Busturia, A (2014) Drosophila p53 controls Notch expression and balances apoptosis and proliferation. Apoptosis19 (10) 1430-43.
  • Fereres,S., Simón, R,  Busturia, A (2013) A novel dRYBP-SCF complex functions to inhibit apoptosis in Drosophila. Apoptosis 18, (12) 1500 -1512.
  • Aparicio, R., Neyen,C., Lemaitre, B., Busturia, A. (2013) dRYBP contributes to the negative regulation of Drosophila IMD pathway. PLoS One Apr 15:8 (4): e62052.

 

Doctoral Theses:

  • Rocio Simón Sacristán (2013). PhD Thesis. Función de las proteínas Polycomb/trithorax y Dp53 en la regulación de la expression génica de Drosophila. PhD Thesis. Universidad Autónoma de Madrid, Spain. Directora: Ana Busturia
  • Sol Fereres Rapoport (2014). PhD Thesis. dRYBP transcription-dependent and transcription-independent functions in Drosophila melanogaster. Universidad Autónoma de Madrid, Spain. Directora: Ana Busturia