Developing DNA "communications"
During embryonic development, gene startup and shutdown are precisely regulated. Gene dynamics endow different cells with different characteristics, allowing embryos to develop into healthy animals in proper proportions. Fgf8 is one of the key genes in this process. It encodes a key signaling factor that controls the growth of limbs and the formation of different regions of the brain. A few days ago, researchers at the European Molecular Biology Laboratory EMBL identified the regulatory modules that control Fgf8 expression during mammalian embryonic development, and clarified the mechanism by which these series of regulatory elements (enhancers) control Fgf8. The article was published in the Cell Development Magazine on February 28. This study emphasizes the importance of genome structure for gene regulation. The researchers found that a series of Fgf8 enhancers are clustered in a large region of the genome. Although some unrelated genes are interspersed between them, these regulatory elements only affect Fgf8. The sequence and arrangement of these elements has been very stable in evolution, which illustrates their importance. Studies have shown that selective changes in the relative positioning of these regulatory elements will change their effect on Fgf8, thereby greatly affecting embryo development. "We found that the complex organization of this genomic region is a key aspect of Fgf8 regulation," said François Spitz, who led the study. "The influence of a specific regulatory element on Fgf8 depends on the specific position of the element, not the sequence of this element. This shows that the influence of promoters on genes in this region does not depend on specific identification tags, but is related to positioning. The article proposes that the structure of this genomic region controls the intrinsic activity of regulatory elements in the region. Scientists are still deeply studying the detailed molecular mechanism of this regulation. They believe that it is likely that under certain conditions, the 3D folding of DNA allows regulatory elements to combine with each other and contact with Fgf8 to activate or prevent gene expression. The level of gene regulation emphasized by the Institute is often easily overlooked, and these regulatory elements do not correspond to specific genes with corresponding sequences one by one. Here, the local organization of the genome and the 3D folding of DNA are actually more important. They not only control the activity of the regulatory element, but also mediate the contact between the regulatory element and the target gene. How the 3D structure of DNA regulates the interaction of genomic elements, and what specific effect it has on the regulation of gene expression, remains to be further studied. These will help us to understand in depth how genome rearrangement affects the aforementioned 3D regulatory network and thus triggers corresponding diseases and malformations.
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