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Newly found CLAMP protein regulates genes
Date:7/18/2013

Soruco and Jessica Chery, and their team of collaborators describe several experiments that demonstrate how CLAMP binds to key sites on the X chromosome and then brings in MSL to those sites to do its work. They first turned up the protein in a wide sweep of the fly genome published last year. They were looking for possible missing link candidates, but hadn't yet figured out from the more than 100 they found which ones were genuinely promising. That process took years more work.

As they began to look more closely at CLAMP, they recognized that it has seven zinc ion-tipped "fingers" for grabbing, or clamping, onto DNA. They also noticed it also has a configuration elsewhere that seemed made for binding to a large protein complex.

In their experiments, both in flies and on the lab bench, they show that CLAMP binds DNA at specific sites known to be relevant for MSL's interaction with the X chromosome. They also showed that interfering with CLAMP prevents MSL from finding the X chromosome.

Positive feedback loop

Then they found something that amazed them. Rather than acting simply as an intermediate link, CLAMP works together with MSL to create a self-reinforcing feedback loop of activity at the X chromosome.

"That was a really big surprise," Larschan said. "I did those experiments myself. I kept doing it again and again because I was so surprised."

One of the more telling analyses took advantage of the sex-specificity of the MSL complex. The researchers noticed that while CLAMP would bind to the X chromosome in both male and female flies, it would only progress past a certain degree in the males. The difference is that males have MSL and females don't.

What the researchers determined is that as a male fly embryo develops, CLAMP binds to some initial sites on the chromosome. That facilitates the assembly of MSL at the chromosome. MSL then opens up the coiled up DNA to expose more sites for CLAMP bind
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Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert

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