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Newly Found CLAMP Protein Regulates Genes

July 15, 2013
Dosage compensation: A male lifeline

“This is the last step of these signaling pathways that make the ultimate regulatory decision about whether you are going to turn on a gene or keep it off,” says Erica Larschan, right, with graduate students Marcela Soruco, left, and Jessica Chery. Credit: Mike Cohea/Brown University

A newly discovered protein, found in many species, turns out to be the missing link that allows a key regulatory complex to find and operate on the lone X chromosome of male fruit flies, bringing them to parity with females. Brown University scientists, including graduate students Marcela Soruco and Jessica Chery helped lead this discovery and name the new protein, CLAMP.

More generally, the research provides biologists with a model of how proteins that govern gene transcription find their targets on chromosomes, a process that’s essential to healthy cell function and sometimes implicated in disease.

The new protein is found in many species including humans. In fly embryos it turns out to be the missing link that brings together the X chromosome and the transcription complex MSL, which doubles the expression of the chromosome. That process, called dosage compensation, brings male flies up to parity with females who have two X chromosomes (in mammals, a similar process downgrades one of the female Xs to ensure parity). In fact, MSL stands for “male-specific lethal” because without it, and without CLAMP, the male flies would die.

Scientists have long puzzled over how MSL and the X chromosome came together, said Erica Larschan, assistant professor of biology in the Department of Molecular Biology, Cellular Biology and Biochemistry and corresponding author of the study published online July 15 in the journal Genes and Development. In fact, she said, they’ve lacked that understanding about many such interactions in which regulatory complexes govern the expression of genes in chromosomes.

Read more of David Orenstein's article on the CLAMP protein.