Magnetic Particle Imaging (MPI) is a promising new tomographic modality for fast as well as three-dimensional visualization of magnetic material. For anatomical or structural information an additional imaging modality such as computed tomography (CT) is required. In this paper, the first hybrid MPI-CT scanner for multimodal imaging providing simultaneous data acquisition is presented.
The reversible acetylation of histone lysine residues
is controlled
by the action of acetyltransferases and deacetylases (HDACs), which
regulate chromatin structure and gene expression. The sirtuins are
a family of NAD-dependent HDAC enzymes, and one member, sirtuin 6
(Sirt6), influences DNA repair, transcription, and aging. Here, we
demonstrate that Sirt6 is efficient at deacetylating several histone
H3 acetylation sites, including its canonical site Lys9, in the context
of nucleosomes but not free acetylated histone H3 protein substrates.
By installing a chemical warhead at the Lys9 position of histone H3,
we trap a catalytically poised Sirt6 in complex with a nucleosome
and employ this in cryo-EM structural analysis. The structure of Sirt6
bound to a nucleosome reveals extensive interactions between distinct
segments of Sirt6 and the H2A/H2B acidic patch and nucleosomal DNA,
which accounts for the rapid deacetylation of nucleosomal H3 sites
and the disfavoring of histone H2B acetylation sites. These findings
provide a new framework for understanding how HDACs target and regulate
chromatin.
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