When egg and sperm¹ combine, the new embryo² bustles³ with（充满） activity. Its cells multiply so rapidly they largely ignore their DNA⁴, other than to copy it and to read just a few essential genes⁶. The embryonic⁷ cells mainly rely on molecular⁸ instructions placed in the egg by its mother in the form of RNA. The cells translate these RNA molecules⁹ into proteins that manage almost everything in the first minutes or hours of the embryo's life. Then, during the so-called midblastula（囊胚） transition, cells start transcribing¹⁰ massive amounts of their own DNA. How embryonic cells prepare for this moment, and how they flag a small set of genes for transcription before that, holds important information about normal development and disease in animals and in humans.

 

A new study that sheds light on these questions appears in the Aug. 13 issue of eLife Sciences, authored by researchers at the Stowers Institute for Medical Research. The team, led by Associate Investigator¹¹ Julia Zeitlinger, Ph.D., shows that in the fruit fly Drosophila melanogaster, genes active in the first two hours of a fertilized¹² egg are read quickly due to special instructions at the beginning of each gene⁵, in a region aptly named the "promoter."

 

Within each promoter region, different combinations of short control elements or "boxes" form a code that instructs specialized¹³ construction crews, called RNA polymerases, where and when to start transcribing. Researchers long thought that once an RNA polymerase appears at the worksite it would quickly finish the job.

 

"The most important result is that promoters are different," Zeitlinger says. "The general paradigm¹⁴ for a long time has been a promoter is a promoter. But really what we see is that they have different functions."

 

As a postdoctoral fellow at MIT, Zeitlinger unexpectedly discovered that sometimes RNA polymerase II pauses at the beginning of a gene as if taking a lunch break. More often than not, pausing occurred at genes important for development. Zeitlinger thought pausing may help get these molecular construction workers on site before a huge work order is due.

 

"We were wondering whether pausing was being used for preparing global gene activation¹⁵ during the midblastula transition," says Kai Chen, PhD, a former graduate student in Zeitlinger's lab and the study's first author. "We expected to see widespread pausing before that transition."

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