Dynamics of BAF- Polycomb Complex Opposition on Heterochromatin in Normal and Oncogenic States

The opposition between polycomb repressive complexes (PRC) and BAF (mSWI/SNF) complexes plays critical roles in development and disease. Mutations in the genes encoding BAF subunits contribute to over 20% of human malignancy, yet the underlying mechanisms remain unclear owing largely to a lack of assays to assess BAF function in vivo. To address this, we have developed a widely applicable recruitment assay system and find that BAF opposes PRC by rapid, ATP-dependent eviction, leading to the formation of accessible chromatin. Reversing this process results in reassembly of facultative heterochromatin. Surprisingly, BAF-mediated PRC eviction occurs in the absence of PolII occupancy, transcription, and replication. Further, we find that tumor suppressor and oncogenic BAF complex mutations result in differential effects on PRC eviction. These studies define a mechanistic sequence underlying the resolution and formation of facultative heterochromatin and demonstrate that BAF opposes polycomb complexes on a minute-by-minute basis to provide epigenetic plasticity

Aiuto medico a morire e diritto: per la costruzione di un dibattito pubblico, plurale e consapevole : documento di sintesi del gruppo di lavoro in materia di aiuto medico al morire

The Document is the result of a disciplinary discussion that the Authors \u2013 legal scholars and professionals with long-standing experience in the related topics \u2013 decided to open on the main legal end-of life issues raised by Order no. 207/2018 of the Italian Constitutional Court, which declared the absolute ban on assisted suicide unconstitutional under certain conditions and called upon the Parliament to regulate the subject. Starting from the \u201cpersonalist\u201d and \u201cpluralist\u201d principles, as well as from the principles of equality and self-determination enshrined in the Italian Constitution, the Document offers a \u201cconstitutionally oriented\u201d and scientific grounded understanding of the wider concept of \u201cmedical assistance to die\u201d. The Document therefore includes some operational proposals on a huge number of tricky issues, such as the prerequisites and conditions to have access to assisted dying, the healthcare professionals involved, the role of the National Healthcare Service, a clear and wellstructured procedure, the regulation of conscientious objection, as well as on issues concerning the source of law to be chosen, the related financial coverage, and the relationships and coordination with other legal rules, including the codes of professional ethics