University of Cambridge > Talks.cam > Cellular Genetic Disease Seminar > Constitutive heterochromatin regulation of genome organisation and stability in mouse embryonic stem cells

Constitutive heterochromatin regulation of genome organisation and stability in mouse embryonic stem cells

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Host: Dr Paolo D'Avino (ppd21@cam.ac.uk)

Constitutive heterochromatin domains (CH) are major contributors to the organization and stability of the genome but the underlying molecular mechanisms remain unknown. Furthermore, the nuclear distribution of CH undergoes massive reorganization during early embryogenesis; terminal differentiation of muscle and brain cells and in tumorigenesis. The establishment and organization of CH loci relies largely on their chromatin identity rather than the underlying DNA sequence. Pluripotent embryonic stem cells (ESCs) have an unusually permissive and hyper-transcribed chromatin, even at typically repressed CH loci, like telomeres and pericentromeres. Furthermore, the clustering of CH into remarkably few and large chromocentres (cytologically defined nuclear domains formed by clusters of pericentromeres from heterologous chromosomes) is one of the hallmarks of ESCs. The prevailing model for this permissive chromatin suggests a role in maintaining genome accessibility and plasticity. In this talk, I will present evidence that an additional function for the open chromatin organisation in ESC is the maintenance of genome integrity through regulation of CH clustering into large chromocentres. I will also explore how ESCs provide a valuable system to study the regulatory mechanisms involved in genome organization and cell state maintenance.

This talk is part of the Cellular Genetic Disease Seminar series.

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