1,062 research outputs found

    Ki-67 Regulates Cell Cycle Progression and Heterochromatin Organization

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    A subset of eukaryotic heterochromatin is located around the nucleoli, and this localization is correlated with gene silencing. Although there is some evidence for trans-acting factors organizing genomic loci around the nucleolus, the characterization of proteins and /or RNAs involved in perinculeolar heterochromatin localization and maintenance is incomplete. Notably, the mammalian female inactive X chromosome, a well-studied model of facultative heterochromatin, frequently resides in the perinucleolar regions during mid to late S phase. The disruption of the Xi–nucleolus association results in the erosion of heterochromatin compartment and silencing, which renders it a good model to investigate the mechanism and biological relevance of heterochromatin organization around the nucleolus. This dissertation will present evidence showing that Ki-67 regulates inactive X (Xi) chromosome association with nucleoli, maintains Xi heterochromatic structures, and regulates cell cycle progression, in cell-type-specific manner dependent on checkpoint proficiency. Ki-67 protein plays roles in heterochromatin organization during interphase. Upon Ki-67 depletion, a subset of Xi in human female hTERT-RPE1 moved away from nucleolus and displayed several features of compromised heterochromatin maintenance. These chromatin alterations were limited to Xi chromosomes localized away from the nuclear lamina and were not observed in virally transformed 293T cells upon Ki-67 depletion. Furthermore, I demonstrated that the different Xi heterochromatin alteration responses result from cell-type-specific reduced proportion of cells in S phase upon Ki-67 depletion. In human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines, depletion of Ki-67 slowed entry into S phase and coordinately downregulated genes related to DNA replication. These cell lines are able to induce p21 expression upon Ki-67 depletion. On the contrary, alteration of transcription and cell cycle progression were not observed in tumor-derived HeLa, U2OS and 293T cell lines. These cell lines do not induce p21 expression either. I additionally examined the Ki-67 function in mouse cell cultures. Depletion of Ki-67 neither redistributes inactive X chromosome nor regulates S phase progression in primary female mouse embryonic cells

    On The Communication Complexity of Linear Algebraic Problems in the Message Passing Model

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    We study the communication complexity of linear algebraic problems over finite fields in the multi-player message passing model, proving a number of tight lower bounds. Specifically, for a matrix which is distributed among a number of players, we consider the problem of determining its rank, of computing entries in its inverse, and of solving linear equations. We also consider related problems such as computing the generalized inner product of vectors held on different servers. We give a general framework for reducing these multi-player problems to their two-player counterparts, showing that the randomized ss-player communication complexity of these problems is at least ss times the randomized two-player communication complexity. Provided the problem has a certain amount of algebraic symmetry, which we formally define, we can show the hardest input distribution is a symmetric distribution, and therefore apply a recent multi-player lower bound technique of Phillips et al. Further, we give new two-player lower bounds for a number of these problems. In particular, our optimal lower bound for the two-player version of the matrix rank problem resolves an open question of Sun and Wang. A common feature of our lower bounds is that they apply even to the special "threshold promise" versions of these problems, wherein the underlying quantity, e.g., rank, is promised to be one of just two values, one on each side of some critical threshold. These kinds of promise problems are commonplace in the literature on data streaming as sources of hardness for reductions giving space lower bounds