The last assignment I'm going to include is my news & views presentation report that I did with Arthi. We presented a paper from Nature, September 2010 by Rolf Ohlsson entitled The Coherent Mediator. This article can be found at http://www.nature.com/nature/journal/v467/n7314/full/467406a.html.
The Coherent Mediator - News and Views
In this news and views article, a paper published by Kagey et al is discussed. The article details the findings of the experiment done. The article focuses on the mediator and cohesin complex. The mediator complex helps enhancers increase gene transcription by bringing together diffusible trans-acting factors and basal transcriptional machinery. The mediator complex also brings together cis-regulatory elements such as enhancers and promoter of active genes. The primary focus of the news and views article is to give evidence on how the mediator achieves this. The recent discovery made by Kagey et al is that the mediator enlists another protein complex cohesin to cohere the enhancer and promoter sequences. The mediator-cohesion complex work together to form a chromatin loop which allows for distal enhancers and promoters to be brought together prior to transcription. The mediator itself interacts with the promoter to stabilize the pre-initiation complex, which positions RNA polymerase II over the start sites of gene transcription. It was also discovered that genes encoding cohesin complex members are also regulators of Oct4 (a regulator for pluripotency in stem cells) expression in embryonic stem cells. Cohesin has been shown to insulate enhancer-promoter communications by aiding in the formation of repressing chromatin loops by CTCF (a transcriptional receptor); however findings by Kagey et al show cohesin localization to regions not possessing CTCF. The discovery of cohesin being involved with in may also have implications on diseases that involve mutations in the mediator complexes.
This article has to do with what we discussed in class in week 4 regarding DNA regulatory sequences. In class, we saw that enhancers, insulators, repressors and locus control regions worked on promoter regions. This was shown using examples that illustrated how enhancers increased gene transcription by acting on promoters and insulators decreased transcription by preventing enhancer-promoter interactions. Specifically, in the transcriptional elements paper by Maston et al that we read that week, we learned that distal upstream regulatory elements (as mentioned) were able to make contact to the core or proximal promoter via a mechanism that loops out intervening DNA between these elements. This article provides insight to the workings of such a mechanism; mediator complex involved in promoter interactions, whether it is with an enhancer or insulator. The article gives us a better understanding of what we learned in class to demonstrate to us how enhancers actually interact with the promoters and what other factors are involved.
We found this article interesting because of the implications these findings (i.e. that cohesin interacts with the mediator complex) has on diseases involved with mediator mutations. As mentioned in the article, schizophrenia (as well as Opitz-Kaveggia (rare genetic syndrome linked to the X chromosome causing physical anomalies and developmental delays) and Lujan syndromes(X-linked genetic disorder that causes mild to moderate mental retardation)) involves mutations involved in the mediator complex. However, with these new findings, it could be shown that cohesin is actually involved in schizophrenia, leading to new treatments for the disorders. As well, gene transcription is one of the most important functions in the human body, the more we know about how it works , the more we are able to find out about how things happen the way they do.
Amanda
email: manda147@interchange.ubc.ca | Student Number: 92681071
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