Cover Image: February 2011 Scientific American Magazine See Inside

The Inner Life of the Genome [Preview]

The way our genes are arrayed and move in the 3-D space of the cell nucleus turns out to profoundly influence how they function, in both health and disease















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Chromosomes in a dividing cell are duplicated and highly compact. At other times, though, they are singletons and more expanded. Until the recent advent of "chromosome painting" techniques, the expanded chromosomes were difficult to distinguish from one another. Image: Illustrations by Anatomy Blue

In Brief

  • Chromosomes are not sprinkled randomly around the inside of the nucleus. They occupy preferred positions.
  • This nuclear organization reflects the functional state of each chromosome and of the genes it carries. The organization can change as a cell’s behavior changes and in disease.
  • Identifying the locations that genes occupy within the nucleus—and seeing how these positions change under different conditions—is providing clues to how normal cells function and how some diseases, including cancer, arise.

More In This Article

Ten years ago publication of the human genome sequence gave the world a blueprint for a human being. But just as a list of automobile parts does not tell us how a car engine works, the complete genome sequence—a list of the DNA “letters” in all the chromosomes of the human cell—did not reveal how the genome directs our cells’ day-to-day activities or allows an individual to develop from a fertilized egg into a functioning adult.

To better understand the way the genome as a whole orchestrates the symphony of biological activity called life, I and others in the new field of genome cell biology are examining how chromosomes, and the genes they house, are arranged within the three-dimensional space of the nucleus and how that organization influences their activities.


This article was originally published with the title The Inner Life of the Genome.



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  1. 1. Dr. Fenn 10:39 PM 2/27/11

    Tom Misteli's is an excellent writer but takes some liberties in 'personifying" genetic mechanics and loses congruency in the use of his facts with his proposition that "nuclear positioning is self-organizing".
    The author clearly has the ability to convey the complex topic of genome cell biology and make it readable. From describing the "architecture" of a chromosome to the basic dynamics of transcription to the burgeoning observation that the gene's specific location in the nucleus is representative of it's likelihood of activity is clearly laid out for the reader.
    There's no question that the use of metaphors is a powerfully effective communication tool. When describing scientific processes, however, it can lead to miscommunicating the objective nature of the chemical, electrical and/or mechanical event. Such statements as "How do genes and chromosomes KNOW where to go-and how do THEY get there...?" assumes these molecules are thinking, intelligent 'beings'. Further characterizations include describing genes s "LOITERING", and "PAYING A VISIT to IT'S FAVORITE transcription factory."
    (Continued Next)

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  2. 2. Dr. Fenn 10:39 PM 2/27/11

    Tom Misteli's is an excellent writer but takes some liberties in 'personifying" genetic mechanics and loses congruency in the use of his facts with his proposition that "nuclear positioning is self-organizing".
    The author clearly has the ability to convey the complex topic of genome cell biology and make it readable. From describing the "architecture" of a chromosome to the basic dynamics of transcription to the burgeoning observation that the gene's specific location in the nucleus is representative of it's likelihood of activity is clearly laid out for the reader.
    There's no question that the use of metaphors is a powerfully effective communication tool. When describing scientific processes, however, it can lead to miscommunicating the objective nature of the chemical, electrical and/or mechanical event. Such statements as "How do genes and chromosomes KNOW where to go-and how do THEY get there...?" assumes these molecules are thinking, intelligent 'beings'. Further characterizations include describing genes s "LOITERING", and "PAYING A VISIT to IT'S FAVORITE transcription factory."

    Although modern genetics persists on promoting the assumption that chromosomes & the protein template fragments, genes, are the all-and-end-all of cellular, tissue, organ and organism "intelligence", we cannot lose our scientific position or poise that energy production, adaptation to our environment, and reproduction may be a reflection of intelligent order but no one component can be "idolized"; given a god-like status as it too has forces acting on it. Even water molecules are subject to and reflecting forces in the environment when crystallizing in the transition from liquid to solid.
    To propose that nuclear positioning is "self-organizing" may be a valid investigational "devil's advocate" stance to take but this rational is not integral with the authors depth of knowledge in biochemical processes. Can "meandering loops" of chromatin be "lucky"? Our current understanding of epigenetics and well-conducted chemical processes of the plasma membrane, the nuclear membrane, the cytoskeletal (spec. microtubules role in organelle movement) transporting processes as well as transporting proteins, provide great fodder for investigating this process. In the end, THERE MUST BE A universal process that assures THAT EACH CELL OF a specific TISSUE PRODUCE THE SAME unique proteins that the tissue is specific for (e.g. mucus for specific epithelial cells, abundant actin & myosin for skeletal muscle cells, etc.). In this way, each tissue type must have the active chromosomes in virtually the same location. If there are approx 220 different tissue types, this is no "LUCK".

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