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A02 - Thomas Braun/Xuejun Yuan:

Delineating the interplay of epigenetic modifiers and transcription factors in the control of muscle stem cell homeostasis and higher order chromatin organization

Epigenetic modifiers play pivotal roles in the control of muscle stem cell (MuSC) homeostasis. We discovered that inactivation of the H4K20 dimethyltransferase Suv4-20h1 in MuSC abrogates formation of facultative heterochromatin (fHC) leading to precocious stem cell activation and rapid tumorigenesis. The aim of the proposed research project is to explore the impact of heterochromatin instability invoked by loss of Suv4-20h1 for the appearance of genomic rearrangements in tumor initiating MuSCs and rhabdomyosarcomas. We will also determine the interplay between Suv4-20h1 and the PRC2 (Polycomb repressive complex-2) complex for modulation of fHC formation and maintenance of MuSC quiescence. Finally, we will unravel the role of histone deacetylase Sirt6 in regulating higher-order chromatin organization in MuSCs.

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