Role and regulation of heterochromatin proteins in the functional organization of the mammalian nucleus

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Proteins and nucleic acids are not freely diffusing in the nucleus but are organized in dynamic higher order structures and subnuclear compartments that form in the absence of dividing membranes. As these subnuclear compartments often correlate with nuclear functions like transcription, RNA processing and DNA replication, these observations led to the concept of the functional organization of the nucleus.We have previously identified several epigenetic regulators that contribute to this functional organization and have identified the responsible regulatory protein domains. Furthermore, we have probed their mobility in the nucleus by fluorescence photobleaching/activation and single molecule tracking.Most recently, we found that HP1 beta and Mecp2 also form phase separated droplets in vitro. We now want to determine the parameters that either promote or prevent droplet formation. Moreover, we want to investigate how the ability of the heterochromatin proteins HP1 beta and Mecp2 to form phase separated droplets in vitro contributes to the functional organization of the nucleus, how posttranslational modifications or interacting factors modulate this process and what functional consequences this property has for the regulation of nuclear functions.