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Articles 1 - 3 of 3

Full-Text Articles in Molecular Biology

Heterogeneity And Intrinsic Variation In Spatial Genome Organization, Elizabeth Finn, Gianluca Pegoraro, Hugo B. Brandao, Anne-Laure Valton, Marlies E. Oomen, Job Dekker, Leonid Mirny, Tom Misteli Aug 2017

Heterogeneity And Intrinsic Variation In Spatial Genome Organization, Elizabeth Finn, Gianluca Pegoraro, Hugo B. Brandao, Anne-Laure Valton, Marlies E. Oomen, Job Dekker, Leonid Mirny, Tom Misteli

University of Massachusetts Medical School Faculty Publications

The genome is hierarchically organized in 3D space and its architecture is altered in differentiation, development and disease. Some of the general principles that determine global 3D genome organization have been established. However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are poorly characterized. Here, we systematically probe the heterogeneity in genome organization in human fibroblasts by combining high-resolution Hi-C datasets and high-throughput genome imaging. Optical mapping of several hundred genome interaction pairs at the single cell level demonstrates low steady-state frequencies of colocalization in the population and independent behavior of individual alleles in single nuclei ...


Ki-67 Contributes To Normal Cell Cycle Progression And Inactive X Heterochromatin In P21 Checkpoint-Proficient Human Cells, Xiaoming Sun, Aizhan Bizhanova, Timothy D. Matheson, Jun Yu, Lihua Julie Zhu, Paul D. Kaufman May 2017

Ki-67 Contributes To Normal Cell Cycle Progression And Inactive X Heterochromatin In P21 Checkpoint-Proficient Human Cells, Xiaoming Sun, Aizhan Bizhanova, Timothy D. Matheson, Jun Yu, Lihua Julie Zhu, Paul D. Kaufman

University of Massachusetts Medical School Faculty Publications

Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here, we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by co-depletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of cell cycle inhibitor p21. Notably, induction of p21 upon depletion of Ki-67 was a ...


Dna-Guided Establishment Of Canonical Nucleosome Patterns In A Eukaryotic Genome, Leslie Y. Beh, Noam Kaplan, Manuel M. Muller, Tom W. Muir, Laura F. Landweber Dec 2014

Dna-Guided Establishment Of Canonical Nucleosome Patterns In A Eukaryotic Genome, Leslie Y. Beh, Noam Kaplan, Manuel M. Muller, Tom W. Muir, Laura F. Landweber

University of Massachusetts Medical School Faculty Publications

A conserved hallmark of eukaryotic chromatin architecture is the distinctive array of well-positioned nucleosomes downstream of transcription start sites (TSS). Recent studies indicate that trans-acting factors establish this stereotypical array. Here, we present the first genome-wide in vitro and in vivo nucleosome maps for the ciliate Tetrahymena thermophila. In contrast with previous studies in yeast, we find that the stereotypical nucleosome array is preserved in the in vitro reconstituted map, which is governed only by the DNA sequence preferences of nucleosomes. Remarkably, this average in vitro pattern arises from the presence of subsets of nucleosomes, rather than the whole array ...