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THIS FOLLOWING SECTION DESCRIBES THE ROLE OF RETROVIRUSES IN CREATING ONE OF OUR MASTER REGULATORY GENES.IT IS IN LAY LANGUAGE.THROUGHOUT THE READING BEAR IN MIND THAT XMRV HAS BEEN FOUND INSERTED INTO CREB__A MAJOR REGULATING GENE IN ITS OWN RIGHT
THERE IS A STING IN THE TALE(not a typo for a change!)
Scientists have long suspected that retroviral elements could play a role in gene regulation. More than 50 years ago, Nobel Laureate Barbara McClintock observed that transposable elements--or "jumping genes"--altered gene expression in maize. In 1971, Roy Britten and Eric Davidson theorized that commonly observed repetitive DNA sequences actually served as codes for gene regulatory networks. The DNA remnants of retroviruses tend to be repetitive sequences and can jump around, when active.
The UCSC team finally gathered concrete evidence to support Britten and Davidson's hypothesis. The group trolled the human genome for ERVs, identified p53 binding sites in them, and tested their ability to activate genes regulated by p53. More than one-third of all known p53-binding sites turned out to be associated with ERVs, they discovered.
These results raise new questions about the role of so-called "junk DNA," the vast regions of the genome that don't code for proteins. ERVs fall into that category. Many scientists once believed that such DNA served no purpose, but new data from the Haussler lab and other labs are challenging that view.
"We're starting to uncover the treasure in this junk," said Wang.
Moreover, the team has proposed a new mechanism for evolutionary change. Conventional wisdom says that evolution is driven by small changes--point mutations--to the genetic code. If a change is beneficial, the mutation is passed onto future generations.
Now it appears that another level of evolution occurs that is not driven by point mutations. Instead, retroviruses insert DNA sequences and rearrange the genome, which leads to changes in gene regulation and expression. If such a change in gene regulation is beneficial, it is passed onto future generations.
This research should have broad implications, according to Wang.
"Our prediction is that this is a general mechanism that has been around ever since viruses," Wang said. "ERV-mediated expansion of a gene regulatory network probably happened more than once and not just in primates. We predict it led to other master gene regulators, not just p53."
Mol Cell Biol. 2000 July; 20(13): 48494858.
PMCID: PMC85936
Copyright 2000, American Society for Microbiology
p53 Recruitment of CREB Binding Protein Mediated through Phosphorylated CREB: a Novel Pathway of Tumor Suppressor Regulation
Holli A. Giebler, Isabelle Lemasson, and Jennifer K. Nyborg*
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870
If XMRV affects the function of creb by creating polymorphic proteins due to insertional mutagenesis
(Silverman et al) then our master gene regulate would not have the same ability to regulate creating a snowball effect
THERE IS A STING IN THE TALE(not a typo for a change!)
Scientists have long suspected that retroviral elements could play a role in gene regulation. More than 50 years ago, Nobel Laureate Barbara McClintock observed that transposable elements--or "jumping genes"--altered gene expression in maize. In 1971, Roy Britten and Eric Davidson theorized that commonly observed repetitive DNA sequences actually served as codes for gene regulatory networks. The DNA remnants of retroviruses tend to be repetitive sequences and can jump around, when active.
The UCSC team finally gathered concrete evidence to support Britten and Davidson's hypothesis. The group trolled the human genome for ERVs, identified p53 binding sites in them, and tested their ability to activate genes regulated by p53. More than one-third of all known p53-binding sites turned out to be associated with ERVs, they discovered.
These results raise new questions about the role of so-called "junk DNA," the vast regions of the genome that don't code for proteins. ERVs fall into that category. Many scientists once believed that such DNA served no purpose, but new data from the Haussler lab and other labs are challenging that view.
"We're starting to uncover the treasure in this junk," said Wang.
Moreover, the team has proposed a new mechanism for evolutionary change. Conventional wisdom says that evolution is driven by small changes--point mutations--to the genetic code. If a change is beneficial, the mutation is passed onto future generations.
Now it appears that another level of evolution occurs that is not driven by point mutations. Instead, retroviruses insert DNA sequences and rearrange the genome, which leads to changes in gene regulation and expression. If such a change in gene regulation is beneficial, it is passed onto future generations.
This research should have broad implications, according to Wang.
"Our prediction is that this is a general mechanism that has been around ever since viruses," Wang said. "ERV-mediated expansion of a gene regulatory network probably happened more than once and not just in primates. We predict it led to other master gene regulators, not just p53."
Mol Cell Biol. 2000 July; 20(13): 48494858.
PMCID: PMC85936
Copyright 2000, American Society for Microbiology
p53 Recruitment of CREB Binding Protein Mediated through Phosphorylated CREB: a Novel Pathway of Tumor Suppressor Regulation
Holli A. Giebler, Isabelle Lemasson, and Jennifer K. Nyborg*
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870
Although coactivator competition is an emerging theme in transcriptional regulation, we have made the fortuitous observation that protein kinase A-phosphorylated CREB strongly enhances p53 association with KIX. Phosphorylated CREB also facilitates interaction of a p53 mutant, defective for KIX binding, indicating that CREB functions in a novel way to bridge p53 and the coactivator. This is accomplished through direct interaction between the bZIP domain of CREB and the amino terminus of p53; a protein-protein interaction that is also detected in vivo. Consistent with our biochemical observations, we show that stimulation of the intracellular cyclic AMP (cAMP) pathway, which leads to CREB phosphorylation, strongly enhances both the transcriptional activation and apoptotic properties of p53. We propose that phosphorylated CREB mediates recruitment of CBP to p53-responsive promoters through direct interaction with p53. These observations provide evidence for a novel pathway that integrates cAMP signaling and p53 transcriptional activity.
(Silverman et al) then our master gene regulate would not have the same ability to regulate creating a snowball effect