Good Luck Amartya!

Amartya Sanyal

Dr. Amartya Sanyal has left the lab to start his own lab at the School of Biological Sciences and Lee Kong Chian School of Medicine at Nanyang Technological University, Singapore. We will miss him, but we are very excited for him!.  Go Amartypedia!

Dr. Sanyal’s website

Two ways to fold the genome during the cell cycle: insights obtained with chromosome conformation capture

two-ways

Genetic and epigenetic inheritance through mitosis is critical for dividing cells to maintain their state. This process occurs in the context of large-scale re-organization of chromosome conformation during prophase leading to the formation of mitotic chromosomes, and during the reformation of the interphase nucleus during telophase and early G1. This review highlights how recent studies over the last 5 years employing chromosome conformation capture combined with classical models of chromosome organization based on decades of microscopic observations, are providing new insights into the three-dimensional organization of chromatin inside the interphase nucleus and within mitotic chromosomes. One striking observation is that interphase genome organization displays cell type-specific features that are related to cell type-specific gene expression, whereas mitotic chromosome folding appears universal and tissue invariant. This raises the question of whether or not there is a need for an epigenetic memory for genome folding. Herein, the two different folding states of mammalian genomes are reviewed and then models are discussed wherein instructions for cell type-specific genome folding are locally encoded in the linear genome and transmitted through mitosis, e.g., as open chromatin sites with or without continuous binding of transcription factors. In the next cell cycle these instructions are used to re-assemble protein complexes on regulatory elements which then drive three-dimensional folding of the genome from the bottom up through local action and self-assembly into higher order levels of cell type-specific organization. In this model, no explicit epigenetic memory for cell type-specific chromosome folding is required.

Dekker, J. (2014). Two ways to fold the genome during the cell cycle: insights obtained with chromosome conformation capture. Epigenetics & chromatin 7, 25.

Nuclear Cartography: Techniques for mapping chromosome conformation

ENCODE

RESEARCHER: Job Dekker, Professor and Co-Director, Program in Systems Biology, University of Massachusetts Medical School, Worcester

PROJECT: Mapping long-range DNA interactions as part of the ENCODE project

PROBLEM: 3C is not easily multiplexed, making its application to large genomic surveys impractical.

SOLUTION: 3C is sometimes called a one vs. one technique because it is used to measure individual interactions between selected pairs of genomic segments. In the technique, cellular chromatin structure is frozen in place with a crosslinker such as formaldehyde. Restriction enzymes cut the DNA and the resulting ends are then ligated together to physically link the two previously separate strands. The crosslink is then reversed to release the now-connected DNA fragments. Finally, researchers probe for specific physical interactions by using PCR to amplify across their ligation junctions.

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