Genome complexity: transcription and DNA structure (Introduction)

by David Turell @, Saturday, September 03, 2016, 00:01 (2786 days ago) @ dhw

Transcription factors and DNA have an intimate relationship for modification of gene expression and function:-http://phys.org/news/2016-09-dna-function-transcription-factors.html-"Substances known as transcription factors often determine how a cell develops as well as which proteins it produces and in what quantities. Transcription factors bind to a section of DNA and control how strongly a gene in that section is activated. Scientists had previously assumed that gene activity is controlled by the binding strength and the proximity of the binding site to the gene. Researchers at the Max Planck Institute for Molecular Genetics in Berlin have now discovered that the DNA segment to which a transcription factor binds can assume various spatial arrangements. As a result, it alters the structure of the transcription factor itself and controls its activity. Neighbouring DNA segments have a significant impact on transcription factor shape, thus modulating the activity of the gene. -***-"The researchers discovered that transcription factors can assume various shapes depending on which DNA segment they bind to. "The shape of the bond, in turn, influences whether and how strongly a gene is activated," Meijsing explains.-"Consequently, transcription factors can bind to DNA segments without affecting a nearby gene.-"One example is glucose production in the liver. If the blood contains too little glucose, the adrenal glands release glucocorticoids, which act as chemical messengers. These hormones circulate through the body and bind to glucocorticoid receptors on liver cells. The receptors simultaneously act as transcription factors and regulate gene activity in the cells. In this way, the liver is able to produce more glucose, and the blood sugar level rises again.-"'Sometimes glucocorticoid receptor binding results in strong activation of neighbouring genes, whereas at other times little if anything changes," Meijsing reports. The scientists found that the composition of DNA segments to which the receptors bind help determine how strongly a gene is activated. However, these segments are not in direct contact with the receptors acting as transcription factors; they only flank the binding sites. Yet, that is evidently enough to have a significant influence on the interaction.-"'The structure of the interface between the transcription factor and genome segments must therefore play a key role in determining gene activity. In addition, adjacent DNA segments influence the activity of the bound transcription factors. These mechanisms ultimately ensure that liver cells produce the right substances in the right amounts," Meijsing says."-Comment: the glucocorticoid example is a wonderful description of how the body is coordinated in its feedback controls of various important chemical levels. I again ask, how did evolution develop such a complex stepwise system of intimate controls. Hard to imagine it is trial and error.


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