Epigenetic Alterations and Loss of Proteostasis

by Georgina Cornwall, PhD

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    Epigenetic alterations, we’ve spent a lot of time thinking about epigenetics in the genetics courses, so epigenetics again above the genome. Traditionally, we consider epigenetic factors to be heritable changes that are not to the DNA but to the way the DNA is packaged and how it is accessed. We know that these epigenetic factors now can change throughout our lives and alter how and when various genes are expressed in the great variety of cells that we have. These changes in chromatin state in essence are regulating the expression of genes. We’ve definitely spoken about epigenetics being one of the factors that regulates gene expression. When we consider epigenetic factors, I think that you could probably write down at least three different epigenetic alterations that could happen. Go ahead and try that out. Then, let’s move forward and look at a quick review of what those are. First of all, we can have histone modifications. Histones are the cores around which DNA is wrapped. Depending on where those histones are located, DNA may be either accessible for transcription or if it’s wound tightly around the histone, inaccessible for gene transcription. These histone modifications can include addition of acetyl groups to the tails and changes in the wrapping of the histone tails, how tightly they hold the DNA onto themselves. Again, that lends itself to accessibility issues on the DNA. Another thing in epigenetic alterations we consider is how methylation patterns happen. You know that areas that are highly condensed heterochromatin, we have tight packing and again, lack of access to genes by the transcriptional mechanisms. There’s a connection of DNA methylation patterns to the development and progression of Alzheimer’s disease and how certain proteins fold in there. We will definitely cover Alzheimer’s disease in a future lecture in a...

    About the Lecture

    The lecture Epigenetic Alterations and Loss of Proteostasis by Georgina Cornwall, PhD is from the course Aging. It contains the following chapters:

    • Epigenetic alterations
    • Loss of proteostasis

    Included Quiz Questions

    1. Heritable changes in phenotype without change in genotype
    2. Changes in genotype without change in phenotype
    3. Inheritable changes in both genotype and phenotype
    4. Changes in DNA without change in chromatin state
    5. Non-inheritable changes in both phenotype and genotype
    1. Loss of proteostasis
    2. Telomere attrition
    3. Spontaneous hydrolytic reaction
    4. Apoptosis
    5. Accumulation of free radicals in the cell
    1. Changes in nucleotide sequences caused by environmental stimuli
    2. Chromatin remodeling caused by environmental stimuli
    3. Changes in patterns of methylation of DNA, altering accessibility for gene transcription
    4. Histone tail modification altering DNA accessibility for gene transcription
    5. An inheritable change in the shape of chromatin without changes to genetic material
    1. Aging cells' loss of proteostasis can lead to common medical conditions in the elderly, such as cataracts.
    2. An aging cell maintains the ability to control the amount of protein it produces.
    3. An aging cell maintains the ability to control the integrity of the protein structure it produces.
    4. Aging cells' loss of proteostasis does not affect the normal signalling between cells.
    5. Aging cell's loss of proteostasis only leads to minimal changes and does not have the potential for toxic accumulation of proteins.
    1. Epigenetic factors can influence how genes are expressed at different ages.
    2. Epigenetic factors do not change throughout our lives.
    3. Epigenetic factors do not change how genes are expressed, they only affect when they are expressed.
    4. Epigenetic alterations are prevented by histone modifications.
    5. DNA methylation patterns are permanent and never change in epigenetic alterations.

    Author of lecture Epigenetic Alterations and Loss of Proteostasis

     Georgina Cornwall, PhD

    Georgina Cornwall, PhD

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