Public release date: 10-Sep-2012 [ | E-mail | Share ]
Contact: Dian Land dj.land@hosp.wisc.edu 608-261-1034 University of Wisconsin-Madison
MADISON The protein GATA2 is known as a "master regulator" of blood cell development. When a mutation occurs in the gene that makes GATA2, serious blood diseases such as acute myeloid leukemia can result.
Zooming in on the GATA2 gene, UW-Madison researchers and their collaborators at the National Institutes of Health (NIH) have discovered unexpectedly that a small DNA sequence drives this powerful master regulator.
The sequence plays an essential role in controlling GATA2 production and generating self-renewing blood stem cells responsible for the earliest steps in the development of blood cells of all kindsred cells to transport oxygen and white cells to fight infection.
The researchers also found that the DNA sequence, which they call the +9.5 GATA2 switch site, ensures that blood vessels function properly to prevent hemorrhaging. Until now, GATA2 had not been implicated in blood vessel integrity. The study appears in The Journal of Clinical Investigation (online Sept. 10, 2012).
Although the study was performed in mice, it should have significant clinical relevance, particularly to physicians and scientists aiming to understand certain types of leukemia and related disorders involving disruptions in the blood and immune systems. The research indicates that downstream genes are impacted when the switch site is altered, leading to abnormal development of the adult blood system, says senior author Dr. Emery Bresnick, professor of cell and regenerative biology at the School of Medicine and Public Health.
"There's every reason to believe that we can use these findings as a foundation to discover key factors and signals that can be modulated therapeutically for the treatment of specific blood and blood vessel disorders," he says.
Bresnick has studied GATA proteins for more than a decade. Among other things, his team discovered five "hot spots" on the GATA2 gene where special activity involving both GATA1 and GATA2 appeared to be taking place. They named these GATA switch sites. Over the last four years, the group has focused on their third GATA2 switch site, +9.5, a small sequence of about 25 base pairs located in a region of the gene called the intron.
"While introns can contain regulatory sequences that control gene activity, until now we and others have been unable to find the mechanisms that control the GATA2 gene, despite years of studying this problem," Bresnick says.
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New genetic mechanism for controlling blood cell development and blood vessel integrity found