Difference between revisions of "KSH 0611 Review Epigenetic modifications regulate gene expression"

From Biolecture.org
imported>Seung-hoon Kim
imported>Seung-hoon Kim
Line 70: Line 70:
 
<h2>Only 2 % of human genome encodes protein and the other 98% controls gene expression by epigenetic mechanism.</h2>
 
<h2>Only 2 % of human genome encodes protein and the other 98% controls gene expression by epigenetic mechanism.</h2>
  
−
<p>&nbsp;</p>
+
<h2>Application</h2>
 +
 
 +
<p>1. Neurological defects could be recovered by correctly recognizing DNA methylation pettern<sup>4)</sup></p>
 +
 
 +
<p>Rett syndrome, one of the severe mental retardation diseases, is mostly caused by <em>MeCP2</em> mutation</p>
 +
 
 +
<p>MeCP2 is a protein that decodes DNA methylated regions. If&nbsp;<em>MeCP2 </em>is mutated, we cannot decode these epigenetic codes.</p>
 +
 
 +
<p>There is a vidio&nbsp;<sup>5) </sup>about&nbsp;recovering mentar redardation by activating normal <em>MeCP2</em> gene using certain chemacals&nbsp;in a mouce.</p>
 +
 
 +
<p>It suggests that we could develop therapies for diverse&nbsp;mental development disorders by studying epigenetics in the future.</p>
 +
 
 +
<p><iframe allowfullscreen="" frameborder="0" height="480" src="//www.youtube.com/embed/RyAvKGmAElQ" width="640"></iframe></p>
  
 
<hr />
 
<hr />
Line 80: Line 92:
  
 
<p>3) Nan, Xinsheng, et al. &quot;Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex.&quot;&nbsp;<em>Nature</em>&nbsp;393.6683 (1998): 386-389.</p>
 
<p>3) Nan, Xinsheng, et al. &quot;Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex.&quot;&nbsp;<em>Nature</em>&nbsp;393.6683 (1998): 386-389.</p>
 +
 +
<p>4)&nbsp;Guy, Jacky, et al. &quot;Reversal of neurological defects in a mouse model of Rett syndrome.&quot;&nbsp;<em>Science</em>&nbsp;315.5815 (2007): 1143-1147.</p>
 +
 +
<p>5)&nbsp;https://www.youtube.com/watch?v=RyAvKGmAElQ&amp;feature=related</p>

Revision as of 14:48, 11 June 2016

 Epigenetics

Definition : Heritable changes in gene activity and expression that occur without alteration in DNA sequence

Different cells control switching on and off in different genes

Two well-known epigenetic modifications

  • Chemical modification to the cytosine residues of DNA (DNA methylation)

DNA methylation usually occurs in cytosine followed by guanine (CpG) by DNA methyltransferase

Most CpG motifs (Repetitive short pattern in DNA sequence or Protein sequence) are located near promoter regions.1)

Promoter is a region of DNA that initiates transcription of a particular gene

The region that has lots of CpG motifs is called CpG island.

Among around 60% of protein-encoding DNA sequences, their promoters are located in CpG islands. 

When a gene is activated, the methylation level of a nearby CpG island is low.

When the gene switches off, the methylation level of the nearby CpG island is high.

MeCP2(Methyl CpG binding protein 2) - acts as a decoder. It only binds to the methylated CpG islands2) and recruits other 'switching off' proteins3).

As a result, DNA is tightly packed and transcription factors cannot access to the promoter region

The methylation pattern is inherited to the daughter cells

​(dna_mdna.png)

(Forschungsbericht_Epicombing_Zillner_figure1.jpg)

(methmaintenence1-e1418413999180.png)

 

  • Histone modification

Why is it important ? >>> Epigenetic  modifications regulate gene activity and expression during development and differentiation, or in response to environmental stimuli

Epigenetics is considered a bridge between genotype and phenotype

Explain how cells carrying identical DNA differentiate into different cell types >>> Epigenetics

Epigenome - global analyses of epigenetic markers across the entire genome

Chromatin - Histone protein / DNA complex in eukaryotic cells

Basic Unit - nucleosome - 146 bp of DNA wrapped around an octamer of the four core histones (H2A, H2B, H3 and H4)

  1. Euchromatin - transcriptionally active state - the region where DNA is accessible due to the relaxed state of nucleosome arrangement
  2. Heterochromatin - transcriptionally inactive state - the area where DNA is packed into highly condensed forms that are inaccessible to transcription factors

How to regulate Protein Synthesis - Epigenetic inheritance controls the amount of the transcribed mRNA. Thus, protein production is regulated.

Ex) Alcohol dehydrogenase (ADH) breaks down alcohol in liver cells.

We could increase the mRNA of ADH  and then make ADH more than usual when we drink much 

Only 2 % of human genome encodes protein and the other 98% controls gene expression by epigenetic mechanism.

Application

1. Neurological defects could be recovered by correctly recognizing DNA methylation pettern4)

Rett syndrome, one of the severe mental retardation diseases, is mostly caused by MeCP2 mutation

MeCP2 is a protein that decodes DNA methylated regions. If MeCP2 is mutated, we cannot decode these epigenetic codes.

There is a vidio 5) about recovering mentar redardation by activating normal MeCP2 gene using certain chemacals in a mouce.

It suggests that we could develop therapies for diverse mental development disorders by studying epigenetics in the future.

Reference

1) Bird, Adrian P. "CpG-rich islands and the function of DNA methylation." Nature321.6067 (1985): 209-213.

2) Meehan, Richard, Joe D. Lewis, and Adrian P. Bird. "Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA."Nucleic acids research 20.19 (1992): 5085-5092.

3) Nan, Xinsheng, et al. "Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex." Nature 393.6683 (1998): 386-389.

4) Guy, Jacky, et al. "Reversal of neurological defects in a mouse model of Rett syndrome." Science 315.5815 (2007): 1143-1147.

5) https://www.youtube.com/watch?v=RyAvKGmAElQ&feature=related

Retrieved from "https://Biolecture.org/index.php?title=KSH_0611_Review_Epigenetic_modifications_regulate_gene_expression&oldid=9517"