June 2011

Gary Felsenfeld: untangling chromatin’s mysteries

Here and Now

Felsenfeld is continuing his own upward trajectory, and recently his group began working on human pancreatic cells. Given that the insulin gene is close to the imprinted Igf2/H19 locus, Felsenfeld has become interested in potential long-range contacts between insulin and other genes mediated by CTCF, and that has led to his most recent findings that the insulin gene's physical proximity with a distant gene's regulatory elements affects that target gene's expression.

  
Imprinting at the IGF2/H19 locus: presence of a CTCF-dependent insulator.

Despite the rapidly changing nature of his work, Felsenfeld has managed to keep a proper focus on the "big picture," an ability that arises from a keen intellectual discipline honed over many years and mentors. "Always keep in mind what you are trying to answer," he says. "Something may seem interesting, but if it's not directly relevant, note it and hope to remember that it exists, but you have to move on.

"Edsall once said, 'I stop outside the atomic nucleus; I've got enough to think about,'" Felsenfeld recalls. "And it's true. You can only do so much!"

In Felsenfeld's case, though, only so much seems to be a lot. This year marks the 50th year of his lab at the NIH, an institution he credits with much of his success. "The NIH Intramural program is one of the few places in the world where I could do science the way I wanted to."

Along the way, Felsenfeld has had the fortune to have great people around him. Foremost would be his family (including three children and eight grandchildren), which has long been a pillar of support. And of course, all the work carried out over those 50 years would not have been possible without a remarkable group of postdocs and grad students. Many of his former protégés now are distinguished researchers in their own right, which provides great pride for Felsenfeld, who considers training young scientists to be one of his most important responsibilities.

And he shows no signs of slowing down.

"Whenever someone asks, 'What's the most exciting thing you've done?' I say, 'What we're doing right now,' because that's all that counts."

References

Xu, Z., Wei, G., Chepelev, I, Zhao, K., and Felsenfeld, G. (2011) Mapping of INS promoter interactions reveals its role in long-range regulation of SYT8 transcription. Nat. Struct. Mol. Biol. 18, 372 – 378.
Wallace, J. A. and Felsenfeld, G. (2007) We gather together: insulators and genome organization. Curr. Opin. Genet. Dev. 17, 400 – 407.
Gaszner, M. and Felsenfeld, G. (2006) Insulators: exploiting transcriptional and epigenetic mechanisms. Nat. Rev. Genet. 7, 703 – 713.
West, A. G., Gaszner, M., and Felsenfeld G. (2002) Insulators: many functions, many mechanisms. Gene. Dev. 16, 271 – 288.
Bell, A. C. and Felsenfeld, G. (2000) Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405, 482 – 5.
Felsenfeld, G. and Rich, A. (1957) Studies on the formation of two- and three-stranded polyribonucleotides. Biochim. Biophys. Acta. 26, 457 – 468.

Angela Hvitved (angela.hvitved@gmail.com) is a freelance science writer.


 

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