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Not All Genes Are Equal; Shortage of Histones Affects Some Genes More Than Others

PLoS Biology
Public Library of Science
Publication Date
DOI: 10.1371/journal.pbio.1001098
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pbio.1001098 1..2 Synopsis Not All Genes Are Equal; Shortage of Histones Affects Some Genes More Than Others Robin Mejia* Freelance Science Writer, Albany, California, United States of America The genome of every human cell com- prises a length of about twometers of DNA. To pack this very long, thin molecule into the microscopic cell nucleus, it must be spooled up very tightly. In the first step of compaction, the DNA molecules wrap around histone proteins to produce nucle- osomes—the dense, bead-like structures commonly thought of as the basic unit of genome packaging. It’s no surprise that this packaging affects the accessibility of the DNA and how it functions. Nucleosomes not only protect the fragile DNA molecules from damage, but also limit the access of other proteins to the DNA, regulating functions like gene transcription. Cells that lack proteins required for histone formation have been shown to be susceptible to genetic damage and early death. New research by Barbara Celona and colleagues at the San Raffaele Scientific Institute in Milan, Italy, shows that when the cell has fewer nucleosomes than usual it affects some genes more than others. The findings run counter to the model that a decreased nucleosome count would be felt equally throughout the genome: in fact, parts of the DNA that normally have high nucleosome concentrations still have high concentrations when the total nucle- osome count drops, whereas sites that normally have lower nucleosome counts tend to lose more of their nucleosomes. The researchers also document the effects of having fewer histones than normal: although yeast and mammalian cells with low histone counts are viable, they are more susceptible to genetic damage and show increased rates of transcription for some genes. To explore the effect of a lower nucle- osome count, the researchers worked with mammalian cells lacking the gene for HMGB1, a high mobility group prote

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