Epigenetic control of haematopoiesis
Cell fate decisions, such as haematopoietic differentiation, are typically initiated by transcription factors that regulate gene expression in concert with epigenetic modifications, which include histone and DNA modifications. DNA methylation related genes including DNMT3A or TET2 are among the most frequently mutated genes in blood malignancies. Traditionally, studies aimed at understanding the effect of aberrant DNA methylation in cancer patients have focused on gene promoters and gene bodies. However, we and others have recently described that the most DNA methylation-dynamic regions are located distally from the genes (at enhancer elements), coinciding with their preferential binding by DNMT3A and TET2. Therefore, how aberrant DNA methylation dynamics impact on the chromatin structure at distal regulatory regions during blood cancer onset and progression remains to be fully elucidated.
Research in our group is aimed to uncover the epigenetic mechanisms governing haematopoietic cell fate decisions, with a special interest in those leading to the onset and development of blood malignancies (including leukaemia and myelodysplastic syndromes among others)
Lines of research:
1. Study of the interplay between DNA (hydroxy)methylation and chromatin dynamics at distal gene regulatory regions during hematopoietic cell fate decisions.
2. Uncovering the role of TET2 in the epigenetic control of the chromatin at distal gene regulatory regions during leukemic onset and progression.
3. Deciphering the molecular mechanisms underlying 5hmC-mediated chromatin compaction during cell fate decisions.
4. Study of the role of mRNA methylation-mediated post-transcriptional control during myeloid cell differentiation.