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Research reveals how dynamic changes in methylation can determine cell fate
Date:9/26/2011

Cold Spring Harbor, NY Scientists at Cold Spring Harbor Laboratory (CSHL) and the University of Southern California (USC) have uncovered intriguing new evidence helping to explain one of the ways in which a stem cell's fate can be determined.

The new data show how the "marking" of DNA sequences by groups of methyl molecules a process called methylation can influence the type of cell a stem cell will become. The cellular maturation process, called differentiation, has long been thought to be affected by methylation. Subtle changes in methylation patterns within subsets of a particular cell type have now been observed and closely scrutinized, and they reveal some intriguing mechanisms at work in the process.

A team led by postdoc Dr. Emily Hodges, working in the laboratory of CSHL Professor and HHMI Investigator Gregory Hannon, studied how methylation changes in blood stem cells can affect whether a given stem cell will differentiate into either a myeloid cell or a lymphoid cell. These are the two major lineages of mature blood cells. Sophisticated mathematical analyses of the data were performed under the direction of USC Professor Andrew D. Smith.

The study, which will appear in print October 7 in the journal Molecular Cell, generated some surprising findings that challenge currently held theories about how methylation operates. First, it demonstrated that methylation patterns are more dynamic than they are often thought to be. "It's not a question of methylation being 'on' or 'off' at a given site in the genome," explains Hodges. "We find, instead, an interesting fluctuation of the boundaries of regions that are free of methylation marks. This fact, in turn, can have a profound impact upon cell fate."

Areas lacking methylation, called hypomethylated regions, or HMRs, tend to coincide with so-called CpG islands, sites in the genome where adjacent "Cs" and "G's" cytosine and guanine nucleotides are see
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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