The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G 2 /M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the levels of H4K20me2/3 throughout the cell cycle. SirT2 binds and deacetylates PR-Set7 at K90, modulating its chromatin localization. Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of H4K20me1. Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 levels, suggesting a novel mitotic checkpoint mechanism. SirT2 loss in mice induces significant defects associated with defective H4K20me1-3 levels. Accordingly, SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis. Our studies suggest that the dynamic cross-talk between the environment and the genome during mitosis determines the fate of the subsequent cell cycle.
This letter shows that, by the proper use of time modulation in equispaced linear arrays with uniform excitation distribution, it is possible to maintain the sidelobe zone of the radiated power under certain-previously stipulated-level whereas the undesired harmonics are minimized. In addition to that, the further extension of the technique to nonequispaced arrays permits to obtain broadband response, by simply searching the positions of the elements that reach to the desired power pattern behavior within the required bandwidth.
Forty‐three dogs affected by canine leishmaniasis (CL) with skin lesions have been studied clinically and histopathologically. Identification of leishmaniads in tissues was achieved using indirect immunoperoxidase staining. According to both macroscopic and microscopic lesions, four different dermatological patterns have been observed. Twenty‐six dogs showed alopecia and desquamation as the main skin lesions. Histologically a diffuse non‐suppurative dermatitis, with numerous leishmaniads inside macrophages was present. Ten animals showed skin ulcerations on limbs, especially over articulations. Histologically, the number of leishmaniads was very reduced. Five animals presented a generalised nodular disease. Each nodule corresponded with a focal accumulation of macrophages, multinucleated giant cells and lymphocytes, with a high number of parasites. Finally, two dogs presented generalised skin pustules. The possible pathogenesis and the differential diagnosis of each form is discussed.
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