Transcriptional regulation mechanisms of POU transcription factors in cancer and their role in homeostasis

The characteristics, functions and fate of cells are determined by the expression of their genes, which is largely controlled by transcriptional regulation. Dysregulation of this process by mutations or failure of the underlying mechanisms leads to disease. Transcription is regulated by epigenetics and chromatin structure as well as by a wide range of transcription factors that function in a coordinated fashion with the basal transcription machinery and dynamic molecular interactions to control cellular programmes.
The POU domain transcription factors play fundamental roles in pluripotency, development and differentiation. As such, their dysregulation or aberrant expression is linked to a variety of diseases.
The aim of this project is the map the regulatory landscape of the main members of this family of transcription factors to unravel the molecular mechanisms by which they control cell behaviour and fate. This consists in identifying the target genes whose expression depends on these factors using technologies as quantitative RT-PCR, RNA sequencing, Chromatin Immunoprecipitation and imaging. with this knowledge the regulation of cellular processes such as proliferation, cell death, DNA repair and differentiation can be assessed. These are processes underlying some of the most common diseases such as cancer and neurodegeneration as well as important physiological reactions such as the immune response and inflammation.

So far, we have identified some targets of POU2f1 (Oct-1) member of this family, with essential roles in immunity: NOS2 and proliferation: Histone 2A and Histone 2B.
We have described the regulatory mechanism by which Oct-1 controls expression of NOS2.
We have identified the aberrant expression of POU2f2 (Oct-2) in some cancer cells and shown that in this context, Oct-2 can dimerise with Oct-1 and modify its activity.