Regulation of Gene Expression

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1
Central dogma of molecular biology
DNA (transcription with RNA polymerase) to RNA to Protein (using ribsosome)
2
Post transcriptional modification is done using  
Post transcriptional modification is done using non-coding RNAs
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Post translational modification is done using  
Post translational modification is done using mRNA modification enzymes
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Methylation can occur at the  and  level
Methylation can occur at the DNA and histone level
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DNA, Histones, Both?
Methylation‐  
DNA, Histones, Both?
Methylation‐ Both DNA and histones
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DNA, Histones, Both?
Acetylation‐  
DNA, Histones, Both?
Acetylation‐ only histones
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DNA, Histones, Both?
Deacetylation –  
DNA, Histones, Both?
Deacetylation – only histones
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Methylation can change the   segment without 
Methylation can change the activity of a DNA segment without changing the sequence
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DNA methylation typically acts to 
DNA methylation typically acts to repress gene transcription
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In DNA methylation
‐ A methyl group is enzymatically added to   via specific 
‐   is usually the recognition sequence
In DNA methylation
‐ A methyl group is enzymatically added to cytosines via specific methyltransferases
‐ CG is usually the recognition sequence
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Methylated bases serve as binding sites for 
Methylated bases serve as binding sites for methyl‐CpG‐binding domain proteins (MGDs)
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MGDs  , , and also recruit  
• DNA methylation usually functions to block transcription
MGDs block transcription factor assembly, block chromatin remodeling, and also recruit histone deacetylases
• DNA methylation usually functions to block transcription
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Methylation is  ‐specific
Methylation is cell and tissue‐specific
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Pattern of methylation is unique in each person and is somewhat influenced by
environment
‐ Total collection of DNA structural alterations =  
Pattern of methylation is unique in each person and is somewhat influenced by
environment
‐ Total collection of DNA structural alterations = epigenetics
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DNA methylation can be used in  
DNA methylation can be used in animal cloning
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In animal cloning, demethylation is  which means that the animals die young because they started with certain genes turned off (similar to in adult)
In animal cloning, demethylation is never complete which means that the animals die young because they started with certain genes turned off (similar to in adult)
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Histone methylation acts to  
Histone methylation acts to repress gene transcription
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Histone methylation occurs on the amino acids
  and   in the histone
protein
Histone methylation occurs on the amino acids
Lysine (K) and Arginine (R) in the histone
protein
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Histone methyltransferases,
transfers methyl groups from  onto the   or
  residues of the  histones
Histone methyltransferases,
transfers methyl groups from S‐Adenosyl
methionine (SAM)
onto the lysine or
arginine residues of the H3 and H4 histones
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Removal of methyl groups is done by  
Removal of methyl groups is done by histone demethylase
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Histone  : the on/off switch for gene expression
Histone acetylation and deacetylation: the on/off switch for gene expression
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Acetylation occurs when   residues with   get acetylated or deacteylated.
Acetylation occurs when lysine residues with N terminal tail get acetylated or deacteylated.
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Acetylation =  
Acetylation = activation
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With   ‐> DNA is released from histone for transcription
With Acetylation ‐> DNA is released from histone for transcription
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With  ‐> DNA packs tightly around histones
With Deacetylation ‐> DNA packs tightly around histones
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Acetylation ‐> the transfer of an acetyl group to a  residue on a histone
• Enzyme ‐>  
Acetylation ‐> the transfer of an acetyl group to a lysine residue on a histone
• Enzyme ‐> histone acetyltransferase (HAT)
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Deacetylation ‐> removal of the acetyl group from the lysine on the histone
• Enzyme ‐> 
Deacetylation ‐> removal of the acetyl group from the lysine on the histone
• Enzyme ‐> histone deacetylase (HDAC)
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Transcription factors are  
Transcription factors are proteins/enzyme
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Gene regulatory transcription factors ‐> proteins that bind to DNA and directly alter the
recruitment/ binding/movement of  and  
Gene regulatory transcription factors ‐> proteins that bind to DNA and directly alter the
recruitment/ binding/movement of basal transcription factors and RNA pol
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Transcription factors are required to   and   for transcription!
Transcription factors are required to bind the promoter and recruit RNA pol for transcription!
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Enhancers and repressors are   that
bind enzymes to  .
Enhancers and repressors are DNA sequences that
bind enzymes to promote or stop transcription.
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DNA‐binding to enhancer bends it to allow for
 
DNA‐binding to enhancer bends it to allow for
transcription.
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Epigenetics
• Alterations to DNA that affect  , but do not
 .
Epigenetics
• Alterations to DNA that affect expression, but do not
change the code.
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The two main components of epigenetics is   and .
The two main components of epigenetics is DNA
methylation
and histone modifications.
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Hypomethylation associated with many  
• the loss of the methyl group in the  
Hypomethylation associated with many cancers.
• the loss of the methyl group in the 5‐methylcytosine
nucleotide
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TEST QUESTION
Epigenetics is a term to describe   and associated alternations in gene expresssion that are   or  
TEST QUESTION
Epigenetics is a term to describe chromatin changes and associated alternations in gene expresssion that are not due to mutation or changes in the DNA sequence
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  >the process by which only one copy of a gene in an individual (either from their mother or their father) is expressed, while the other copy is suppressed. This impacts  .
Imprinting >the process by which only one copy of a gene in an individual (either from their mother or their father) is expressed, while the other copy is suppressed. This impacts transcription.
38
What is Prader-Will syndrome? What is missing? What does it cause?
-Genomic impriting in humans
-Small region in long arm of chromosome 15 is missing from FATHER
-People feel a constant state of hunger
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What is Angelman syndrome? What is missing? What does it cause?
-Genomic imprinting
-It is also due to a small region in long arm of chromosome 15 is missing from MOTHER
-Frequent laughter, large mouth
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What is Silver-Russel syndrome? What chromosome is impacted? What does it cause?
Change in chromosomes 7 or 11 in about 60% of people with the condition
• genes that control growth
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What is Beckwith-Wiedemann syndrome? What chromosome is impacted? What does it cause?
-Caused by changes on chromosome 11p15. 5
-Overgrowth syndrome
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Lifestile and diets can affect epigenetics because they can be  
Lifestile and diets can affect epigenetics because they can be methyl donors.
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In the study done on the men with protsatse cancer, intense changes in life-style were seen to cause  (RAN) and  was upregulated (ZNF250)
In the study done on the men with protsatse cancer, intense changes in life-style were seen to cause cancer downregulation (RAN) and new protein building was upregulated (ZNF250)
44
Transcendental Meditation (or just plain rest for 20
mins/day) alters  
Transcendental Meditation (or just plain rest for 20
mins/day) alters telomerase expression
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