Epigenetic, genetic and maternal effects enable stable centromere inheritance

Centromeres are defined epigenetically by the histone H3 variant CENP-A. The propagation cycle by which pre-existing CENP-A nucleosomes serve as templates for nascent assembly predicts the epigenetic memory of weakened centromeres. Using a mouse model with reduced levels of CENP-A nucleosomes, we find that an embryonic plastic phase precedes epigenetic memory through development. During this phase, nascent CENP-A nucleosome assembly depends on the maternal Cenpa genotype rather than the pre-existing template. Weakened centromeres are thus limited to a single generation, and parental epigenetic differences are eliminated by equal assembly on maternal and paternal centromeres. These differences persist, however, when the underlying DNA of parental centromeres differs in repeat abundance, as assembly during the plastic phase also depends on sufficient repetitive centromere DNA. With contributions of centromere DNA and the Cenpa maternal effect, we propose that centromere inheritance naturally minimizes fitness costs associated with weakened centromeres or epigenetic differences between parents. © 2022, The Author(s), under exclusive licence to Springer Nature Limited

Eigenpolytopes Of Distance Regular Graphs

Let X be a graph with vertex set V and let A be its adjacency matrix. If E is the matrix representing orthogonal projection onto an eigenspace of A with dimension m, then E is positive semi-definite. Hence it is the Gram matrix of a set of jV j vectors in R m . We call the convex hull of a such a set of vectors an eigenpolytope of X. The connection between the properties of this polytope and the graph is strongest when X is distance regular and, in this case, it is most natural to consider the eigenpolytope associated to the second largest eigenvalue of A. The main result of this paper is the characterisation of those distance regular graphs X for which the 1-skeleton of this eigenpolytope is isomorphic to X

Specifying and reasoning about dynamic access-control policies

Abstract. Access-control policies have grown from simple matrices to non-trivial specifications written in sophisticated languages. The increasing complexity of these policies demands correspondingly strong automated reasoning techniques for understanding and debugging them. The need for these techniques is even more pressing given the rich and dynamic nature of the environments in which these policies evaluate. We define a framework to represent the behavior of accesscontrol policies in a dynamic environment. We then specify several interesting, decidable analyses using first-order temporal logic. Our work illustrates the subtle interplay between logical and state-based methods, particularly in the presence of three-valued policies. We also define a notion of policy equivalence that is especially useful for modular reasoning.

Aurora A kinase phosphorylates Hec1 to regulate metaphase kinetochore-microtubule dynamics

Precise regulation of kinetochore-microtubule attachments is essential for successful chromosome segregation. Central to this regulation is Aurora B kinase, which phosphorylates kinetochore substrates to promote microtubule turnover. A critical target of Aurora B is the N-terminal "tail" domain of Hec1, which is a component of the NDC80 complex, a force-transducing link between kinetochores and microtubules. Although Aurora B is regarded as the "master regulator" of kinetochore-microtubule attachment, other mitotic kinases likely contribute to Hec1 phosphorylation. In this study, we demonstrate that Aurora A kinase regulates kinetochore-microtubule dynamics of metaphase chromosomes, and we identify Hec1 S69, a previously uncharacterized phosphorylation target site in the Hec1 tail, as a critical Aurora A substrate for this regulation. Additionally, we demonstrate that Aurora A kinase associates with inner centromere protein (INC ENP) during mitosis and that INC ENP is competent to drive accumulation of the kinase to the centromere region of mitotic chromosomes. These findings reveal that both Aurora A and B contribute to kinetochore-microtubule attachment dynamics, and they uncover an unexpected role for Aurora A in late mitosis