Release date: 2013-01-22

How does the huge diversity of the animal world evolve from a limited gene pool? The mouse has been an effective model for medical research because it shares 80% of the protein-coding genes with humans. More and more scientific evidence shows that the key to the amazing complexity of nature is the regulation of gene expression by transcription factors. Now, researchers at the US Department of Energy's Lawrence Berkeley Laboratory and the University of California at Berkeley have discovered the secrets of key transcription factors that regulate gene expression through structural transformation. Researchers led by biophysicist Eva Nogale found that TFIID transcription factors coexist in two different structural states by single-particle cryo-electron microscopy. The two states (standard state and rearrangement state) differ only in the translocation of a substructural element, lobe A, which converts transcription, and transcribes the genetic information of the DNA into RNA for protein synthesis. . “TFIID can fluctuate between standard and reordered states,” said Nogales, the author of the article, top SEM expert. "When TFIID binds to another transcription factor, TFIIA, it mainly shifts to the standard state. But when both TFIIA and DNA are present, TFIID turns into a rearrangement state to recognize and bind key DNA sequences, which also marks the beginning of the transcription process. Transcription is a key process in the growth, development and survival of organisms. Studying the structural transformation of TFIID and its role in transcription helps to further understand the regulation of gene expression. As more and more organisms' genomes are sequenced, it has been found that the total number of genes in the genome does not reflect the complexity of the organism. For example, fruit flies are much more complex than Caenorhabditis elegans, but their genes are about 6,000 less than nematodes. The fruit fly genome has about 20,000 genes, and it is speculated that the total number of human genes is between 30,000 and 40,000. There are about one thousand transcription factors that regulate gene expression in Drosophila and C. elegans, and there are almost three thousand humans. These transcription factors often function in a variety of combinations, resulting in greater complexity. "Although the number of protein-coding genes is relatively stable during the evolution of multicellular animals, the number of DNA regulatory elements is increasing significantly," Nogales said. "We found that TFIID exists in two structural and functional forms, demonstrating the mechanism by which transcription factors combine to regulate gene expression levels and thereby increase diversity." Nogales and colleagues first obtained three-dimensional binding of human TFIID to DNA by single-particle cryo-electron microscopy. Image. “We found the TFIID to be as flexible as its lobe A area, which is about one-third of the complex, and this area can translocate 100 angstroms,” said Michael A. Cianfrocco, the first author of the article. "The lobe A translocation is required for TFIID binding to DNA." TFIID tends to be standard in the absence of DNA, at which point lobe A of TFIID binds to lobe C. In the reconfiguration, TFIID's lobe A is combined with lobe B to enable TFIID to bind firmly to the DNA promoter. "TFIIA molecules mediate this translocation process, and TFIIA maintains the standard state of TFIID in the absence of DNA, and it helps initiate the reconfiguration of TFIID when the DNA promoter appears," Cianfrocco said. "Without the presence of TFIIA, the binding of TFIID to DNA is weak." Nogales and colleagues are investigating how TFIID binds to DNA to recruit other proteins needed for gene transcription. “This includes building macromolecular complexes of more than two million daltons, almost as large as bacterial ribosomes,” Nogales said. "The size and relative instability of this complex will be the main challenge for the experiment."

Source: Cell

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