Post Doctoral Fellowships
Karen Monier, Ph.D.
The Scripps Research Institute
"Role of MeCP2 in the formation of centric heterochromatin compartments in neurons."
Mentor: Kevin F. Sullivan, Ph.D.
2-Year Award: $90,000
Lay Final Report (November, 2002)
During my two-year fellowship I depicted in great details the nuclear core anatomy of cells devoted to become brain cells. Because of their potential relationship with Rett Syndrome, my focus was on specific regions involved in keeping gene silenced and thus preventing proteins to be produced. I found that the composition of those regions is not everlasting but is rather well modified during the course of the cell cycle or the course of neuronal differentiation. When cells were pushed towards neuronal differentiation they underwent a dynamic nuclear reorganization over few weeks, associated with MeCP2 expression and a nuclear redistribution of the potential binding sites of MeCP2. My results suggest that the flavor of silenced regions is different in brain cells and is finely tuned by the presence of MeCP2 to keep gene silenced. The absence of a functional MeCP2 that cannot bind to methylated DNA or recruit a repressor will change this delicate balance toward permissive gene activation and therefore modify the neuronal pattern of gene expression. This model supports gene silencing defects in Rett Syndrome patients and provides insights into its mechanistic basis.
Karen Monier, Ph.D.The Scripps Research Institute
"Role of MeCP2 in the formation of centric heterochromatin compartments in neurons."
Mentor: Kevin F. Sullivan, Ph.D.
2-Year Award: $90,000
Lay Final Report (November, 2002)
During my two-year fellowship I depicted in great details the nuclear core anatomy of cells devoted to become brain cells. Because of their potential relationship with Rett Syndrome, my focus was on specific regions involved in keeping gene silenced and thus preventing proteins to be produced. I found that the composition of those regions is not everlasting but is rather well modified during the course of the cell cycle or the course of neuronal differentiation. When cells were pushed towards neuronal differentiation they underwent a dynamic nuclear reorganization over few weeks, associated with MeCP2 expression and a nuclear redistribution of the potential binding sites of MeCP2. My results suggest that the flavor of silenced regions is different in brain cells and is finely tuned by the presence of MeCP2 to keep gene silenced. The absence of a functional MeCP2 that cannot bind to methylated DNA or recruit a repressor will change this delicate balance toward permissive gene activation and therefore modify the neuronal pattern of gene expression. This model supports gene silencing defects in Rett Syndrome patients and provides insights into its mechanistic basis.