Study reveals key aspect of finely tuned regulation of gene expression – ScienceDaily


Your skin cells are very different from your brain cells even though they develop in the same person and carry the same genes. They are different because each type of cell expresses a specific set of genes that differ from those expressed by the other. This is possible thanks to cellular mechanisms that tightly regulate gene expression.

In a study published in Proceedings of the National Academy of SciencesBaylor College of Medicine researchers in Dr. Bert O’Malley’s group have revealed a key new aspect of the mechanism of gene expression regulation. The findings not only contribute to a better understanding of this fundamental biological process, but also open up new possibilities for studying changes in the regulation of gene expression that lead to disease.

“Gene expression is controlled at different levels,” said lead author Dr. Anil Panigrahi, assistant professor in the Department of Molecular and Cellular Biology at Baylor. “In this study, we focused on enhancers, which are a critical component that regulates gene expression. Enhancers are segments of DNA that activate gene expression by interacting with the promoter of a gene. Enhancers and promoters form a physical connection, which relays the message to the cell of when to express About the gene and its amount.

Although it seems that the boosters and promoters coordinate their actions, it is not clear how this happens. In this study, Panigrahi and colleagues propose a mechanism that explains the close relationship between reinforcers and promoters.

Enhanced regulation of gene expression has been studied mostly in healthy living cells. “However, despite learning a lot from these systems, it is difficult to control specific components in healthy cells, which limits our mechanistic understanding of the process,” Panigrahi said. “For this reason, we designed a cell-free assay that enables us to control the availability of different reaction components and determine how this affects transcription.”

“In the cell-free system, we’ve seen that enhancer and promoter communicate closely physically when a gene is doing transcription, that is, making mRNA copies of a DNA sequence,” said Panigrahi. “But we discovered that not only the gene but also the enhancer is transcribed in the cell-free system, as it is in living cells.”

Furthermore, they found that enhancer transcription mirrored promoter transcription. “If we know the transcription state of the enhancer, then we know the transcription state of the enhancer and vice versa,” Panigrahi said. “If we delete the promoter, transcription of the enhancer will be significantly reduced and vice versa. Enhancer and transcription of the promoter are tightly interconnected.”

Previous studies using cell-based assays suggested that enhanced transcription somehow activates inducible transcription.

“What we’re saying is this goes both ways, not just one,” Panigrahi said. “Enhancer transcription activates promoter transcription and vice versa. Not only that, if the amount of transcription in the enhancer is reduced, transcription of the enhancer will also be reduced and vice versa. There is transcriptional interdependence between enhancers and promoters, which was not previously known.”

The authors suggest that such regulatory interdependence and specificity could be explained if the enhancer and promoter are intertwined within a transcriptional bubble that provides shared resources for transcription and is regulated by the levels of transcription generated.

said O’Malley, chair of the division of molecular and cellular biology and co-director of basic research at the Duncan Comprehensive Cancer Center at Baylor. “Our cell-free assay can be used to study promoter-enhancer interactions for any gene of interest, whether in health or in disease.”

David M. Lonard of Baylor also contributed to this work.

This study was supported by National Institutes of Health grants HD007875 and HD08818.



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