Impact of Chromatin on Transcription

by Georgina Cornwall, PhD

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    00:00 That is a lot about how we could modulate the level of transcription of our DNA in order to provide a primary transcript. But before that even happens, what about how DNA is packed? If it is packed up really tightly, we cannot really even access the DNA. Let us have a quick review of how the DNA is packed. We have got our linear DNA and its wrapped around nucleosome couple of times to quarter times and is anchored on with an H1 histone and then it is like beads on a string and if we drop those beads on a string into a tall column, they all stuck up together like this figure and then that coil, well that stacking of beads on a string will then coil and then it will supercoil and then the supercoils will all stack together to form our eventual chromosome.

    01:00 Now if it is in this chromosome form like it would be during cell division, then we probably can't really read any of the genes on that DNA. A certain amount of uncoiling is necessary and we can see that the association with the nucleosome has a lot to do with whether DNA can be expressed or not. For example, if our nucleosome is hanging out, it has got its two and a half turns of DNA and it is all happy those histone tails are going to hold onto the DNA and hold it fairly tight. But if we add acetyl groups, if there are lots of acetyl groups around that can attach to those histone tails, then the histone tails are all willy nilly and they cannot hold on to the DNA quite as tightly and that on its own gives access to RNA polymerase to perhaps transcribe the genes. This is one of those epigenetic factors something above the genome that could affect gene expression. And many factors could affect how epigenetic factors manifest themselves and I have a whole section that we talk about epigenetics, so I hope that I see you in that lecture. Anyway, when these acetyl groups are on there, the DNA is less well packed and again we can have transcription because of the less well packing.

    02:31 This doesn't take any energy just acetyl groups to be around and attach to the histone tails.

    02:38 It was previously thought that methylation of DNA was what really prevented transcription of certain regions that were fairly well unwound. However, now we realized that the methylation is probably less primary than some other mechanisms and it is there as more of a protecting factor to make sure that things that have already been turned off don't accidentally get transcribed.

    03:04 Again previously we thought methylation was it, as we learn more and more in science and biology, genetics, we are learning that there are many other mechanisms that come into play.

    03:17 For example, we could look at some of these chromatin remodeling factors. These are fairly recent discoveries that there are some factors out there that are energy dependent and those factors can alter how DNA is wound around the nucleosome. Different than acetylation because we require energy, but it could allow the nucleosome to slide along the DNA and allow access to RNA polymerase and all of those other transcriptional mechanisms, upstream of where the nucleosome was so that DNA was wound round a nucleosome because the nucleosome slid. It is no longer wrapped up and it is accessible. We could also see that the nucleosome itself could be remodeled so other proteins that are energy dependent come along and move pieces of the nucleosome and sort of unraveled the DNA providing again more access. Other things that can happen is the nucleosome could simply be removed. We put in a little energy, some factor probably another enzyme comes along unwinds it temporarily and says "Hey! Time to transcribe here." Then we could have actual histone replacement. It has been noted that some normal histones will come out and another type of histone will go in and it may impact gene expression. Lots of different things could be going on at the level of DNA packing, some dependent on energy and some not.

    About the Lecture

    The lecture Impact of Chromatin on Transcription by Georgina Cornwall, PhD is from the course Gene Regulation.

    Included Quiz Questions

    1. Once a gene is turned off, it will remain off.
    2. The nucleosome will quickly form, which assists in mRNA formation.
    3. Once that gene is transcribed, the mRNA is saved and used over and over again.
    4. The gene functions without interruption.
    1. RNA methylation
    2. Nucleosome sliding
    3. Remodeled Nucleosome
    4. Nucleosome removal
    5. Histone replacement
    1. …facilitates the decondensation of chromatin and allows DNA transcription.
    2. …facilitates the condensation of chromatin to allow chromosome formation.
    3. …prevents the decondensation of the chromosome.
    4. …prevents the binding of the transcriptional factors and activators to the gene.
    5. …participates in the tight coiling of DNA duplex around the histone core.

    Author of lecture Impact of Chromatin on Transcription

     Georgina Cornwall, PhD

    Georgina Cornwall, PhD

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