Pushmi-pullyu of B-cell development ...( Although every cell in the body carr...)

Although every cell in the body carries the genes necessary to function as an antibody-producing B cell, only a small proportion of stem cells mature into those important immune-system cells. James Hagman, PhD, Professor of Immunology at National Jewish Health and his colleagues have identified two "molecular motors" that work in opposing directions to control the development of B cells. They published their findings June 19 in the online version of The Proceedings of the National Academy of Sciences USA.

"We found that these two 'chromatin remodeling complexes' work in a sort of pushmi-pullyu manner to induce or retard epigenetic changes that allow for the development of a B cell," said Hagman. The pushmi-pullyu was a fictional animal in the Dr. Doolittle stories that had a head at opposite ends of its body, each pulling in a different direction. "The complexes help control both the unspooling of DNA to make genes accessible and the demethylation of DNA that removes silencing markers."

Although DNA in every cell contains the genes necessary to become B cells, two factors help keep them silent. One is the fact that the two meters of DNA inside a tiny cell nucleus is wrapped around millions of tiny spools, linked together like a string of pearls, which help keep the hereditary molecule from becoming irretrievably tangled. When wrapped tightly around these spools, individual genes are inaccessible to the molecules that bind and activate them. Second, many of the genes have small methyl groups, a carbon and three hydrogen atoms (CH3), on their DNA in specific places, which also prevent them from being activated. These factors are considered epigenetic states, modifications to existing DNA that control their activation or silencing.

Dr. Hagman and his colleagues previously identified a protein, known as Early B-cell Factor or EBF, which they dubbed a 'pioneer factor.' By altering the epigenetic state of several genes, it is estimate
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