HP1 Recruits Activity-Dependent Neuroprotective Protein to H3K9me3 Marked Pericentromeric Heterochromatin for Silencing of Major Satellite Repeats

H3 lysine 9 trimethylation (H3K9me3) is a histone posttranslational modification (PTM) that has emerged as hallmark of pericentromeric heterochromatin. This constitutive chromatin domain is composed of repetitive DNA elements, whose transcription is differentially regulated. Mammalian cells contain three HP1 proteins, HP1α, HP1β and HP1γ These have been shown to bind to H3K9me3 and are thought to mediate the effects of this histone PTM. However, the mechanisms of HP1 chromatin regulation and the exact functional role at pericentromeric heterochromatin are still unclear. Here, we identify activity-dependent neuroprotective protein (ADNP) as an H3K9me3 associated factor. We show that ADNP does not bind H3K9me3 directly, but that interaction is mediated by all three HP1 isoforms in vitro. However, in cells ADNP localization to areas of pericentromeric heterochromatin is only dependent on HP1α and HP1β. Besides a PGVLL sequence patch we uncovered an ARKS motif within the ADNP homeodomain involved in HP1 dependent H3K9me3 association and localization to pericentromeric heterochromatin. While knockdown of ADNP had no effect on HP1 distribution and heterochromatic histone and DNA modifications, we found ADNP silencing major satellite repeats. Our results identify a novel factor in the translation of H3K9me3 at pericentromeric heterochromatin that regulates transcription

Insight into the effect of Ti-addition on diffusion-controlled growth and texture of Nb 3 Sn intermetallic superconductor phase

The alloying of Ti with Cu(Sn) and Nb significantly increases the grain boundary diffusion-controlled growth kinetics of Nb 3 Sn accompanied with a decrease in the activation energy in the Cu(5.5 at. Sn, Ti)/Nb and Cu(5.5 at. Sn)/Nb(Ti) diffusion couples. In either case, the β-(Ti,Nb) precipitates form at the grain boundaries of Nb 3 Sn. On the other hand, the ternary intermetallic phase, Nb 3 Sn 2 Ti 3 , is present in the interior of the Nb 3 Sn phase matrix only when Ti is added to Nb. The pinning forces on the grain boundaries of Nb 3 Sn exhorted by the β-(Ti,Nb) precipitates and related microstructure refinement results in an enhanced growth kinetics of the product phase, Nb 3 Sn. The addition of 0.5 at. Ti to Cu(Sn) has a stronger influence on the growth kinetics and the activation energy for the growth of Nb 3 Sn compared to 3 at. Ti to Nb owing to a higher fraction of smaller and equiaxed grains with high angle grain boundaries of Nb 3 Sn. The Ti-free Nb 3 Sn phase layer grows with a weak texture, a commonly observed behavior in other material systems for the product phases grown by diffusion-controlled mechanism in the interdiffusion zone. On the contrary, a very strong crystallographic texture of the Ti-containing product phase, Nb 3 Sn, is reported that has a unique pattern depending on the orientation of the adjacent Nb or Nb(Ti) grains. The Cu atoms segregate to the grain boundaries of Nb 3 Sn over a distance of �2�5 nm with a depletion of Nb. © 201