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Nestled inside the human genome, there may be another secret code waiting to be deciphered. The human genome is now thought to contain 22,000 or so genes that code for proteins, the building blocks of life. But how are such a small number of genes programmed to embark on widely different paths of development?

Michael LevineNestled inside the human genome, there may be another secret code waiting to be deciphered. The human genome is now thought to contain 22,000 or so genes that code for proteins, the building blocks of life. But how are such a small number of genes programmed to embark on widely different paths of development? In other words, says UC Berkeley molecular and cell biologist Michael Levine, "what puts your head on top of your shoulders and not in your rear end?" To answer that question, Levine has spent several decades reigning over his genetics laboratory as lord of the flies.

"Flies may be small, but they're up there with vertebrates in terms of complexity," Levine says. "I'm a fly guy for life."

Indeed, Drosophila, the common fruit fly, is ideally-suited for Levine's experiments that provide insight into the mind-boggling intricacies of fetal development. The researchers focus on the second hour of a fly's embryonic life. That's when the cells begin to differentiate into various parts of the fly tissue and the signs of regulatory DNA are first revealed. Regulatory DNA, Levine explains, controls how and where a gene is expressed in a cell. Of the three types of regulatory DNA--enhancer, silencer, and insulator--"enhancers are king, activating gene expression in specific cell types for specific tissues," he says. Scientists conservatively estimate that while the human genome has less than 30,000 genes, it may contain 100,000 enhancers at the minimum. So far, just 50 or so have been identified.

"It's hard to come up with an accurate estimate because they're so elusive," Levine says. "You can take an unknown genome and find a protein-coding gene just by reading the code. You may not know a thing about the gene, but at least you can identify it. So far though, we haven't found the code for regulatory DNA, if one even exists."

In recent years, Levine has leveraged computational methods to sift through genetic data in search of binding sites within certain genes that may be indicative of a "landing pad" for enhancers. As his research group continues to build a dataset of possible enhancers, they've also begun to examine enhancers function. Specifically, how does an enhancer activate a gene when it maps thousands of base pairs of DNA away?

Read the complete article at ScienceMatters