Introduction
Regulation of transcription
The hematopoietic stem cell (HSC) is responsible for the formation of all blood cell lineages both in the embryo and the adult. HSC differentiation and lineage specification involve activation and repression of specific transcription programs. This is achieved by the coordinated action of conserved key transcription factors (TF). Our aim is to identify and characterize these TFs and to unravel their complex organization during blood cells differentiation. We also aim at understanding how erythroid genes get sequentially activated and repressed throughout development. Particular emphasis is given to the regulation of the β globin gene locus both as a model system to study the three dimensional organisation and interactions between regulatory regions at the molecular level and as a system that is responsible for β thalassemia and sickle cell anaemia. These two diseases are among the most widespread genetic diseases in the world and we are interested in exploiting the process of globin gene switching with the eventual aim to treat patients suffering from these diseases.
In order to achieve these goals we use a combination of state of the art technologies involving proteomic tools (protein tagging, single-step purification of TF complexes, mass spectrometry), genome-wide analysis of TF binding sites (chromatin immunoprecipitation coupled to high throughput sequencing, ChIP on chip, expression microarray analysis), RNAi library screens, and in vivo functional studies (mouse knock-in/knock out, morpholino-mediated knockdown of gene expression in zebrafish).
Contact information
Prof. Frank Grosveld
Department of Cell Biology
Dr. Molewaterplein 50
3015 GE Rotterdam
or
POB 2040
3000 CA Rotterdam
The Netherlands
e-mail : f.grosveld@erasmusmc.nl