Kati Sriwiyati MBK 155010070: Epigenetics - Biochemistry (Juny 11, 2015)

Kati Sriwiyati
MBK 155010070
Epigenetics - Biochemistry (Juny 11, 2015)

 C.H. Waddington coined the term epigenetics to
mean above or in addition to genetics to explain
differentiation.
 How do different adult stem cells know their fate?
◦ Myoblasts can only form muscle cells
◦ Keratinocytes only form skin cells
◦ Hematopoetic cells only become blood cells
◦ But all have identical DNA sequences.

Epigenetics - Biochemistry (Juny
11, 2015)
 Epigenetics refers to the study of changes in the
regulation of gene activity and expression that
are not dependent on gene DNA sequence.
 While epigenetics often refers to the study of

single genes or sets of genes, epigenomics
refers to more global analyses of epigenetic
changes across the entire genome.

11, 2015)
11, 2015)
11, 2015)
11, 2015)
Non-coding RNA
(RNA based mechanism)
Gene Expression
DNA Methylation
Histone Modifications

11, 2015)
 Adding methyl group to the DNA, mostly at
CpG sites, that convert cytosine to 5-
methylcytosine by DNMT1 (DNA
Methyltransferase) enzyme.
 Hypomethylated gene  activated oncogen
and initiate chromosome instability.
 Hypermethylated gene  initiate silencing of
tumor suppressor gene

 Mechanisms for repression by DNA
methylation:
◦ Inhibits DNA binding by transcription factors
◦ Mehyl binding proteins recruit co-repressors
◦ DNMTP enzymes recruit histone modification
enzymes

11, 2015)
Hypomethylation
Hypermethylation
http://www.cellscience.com/reviews7/Taylor1.jpg
11, 2015)
11, 2015)
Paula Vertino, Henry Stewart Talks
11, 2015)
11, 2015)
Transcription factors
RNA polymerase
Transcription Acetylation
DNA 5-methyl-C
methyltransferase
Methyl-CpG Histone deacetylase

Binding proteins
and associated
co-repressors
Transcription blocked
Deacetylation
X
Chromatin compaction
Transcriptional silencing
Alex Meissner, Henry Stewart Talks 11, 2015)
11, 2015)
John Greally, Henry Stewart Talks
Me

11, 2015)
 Cancer
 Mental retardation disorders  ATR-X,
Fragile-X, Prader-Willi and Angelman
syndrome.
 Neuropsychiatric disorder  Alzheimer,
schizophrenia, etc
 Autoimmune disease  Lupus

11, 2015)
Robertson,
Epigenetics Nature Reviews
- Biochemistry (Juny Genetics, Vol6, 597
11, 2015)
 A nucleosome contains :
◦ A nucleosome core particule
 146 base pairs of supercoiled
DNA
 Around a core of eight histones
◦ Histone core
 2 copies of H2A,H2B, H3, and
H4
 H1 resides outside of core
 Linker histone
 Binds to linker DNA
 Connecting one nucleosome to
next
11, 2015)
 Histone modifications : activate or silence
transcription
 By directly controlling the accessibility of DNA
to the transcriptional machinery (Lysine
acetylation)
 By recruiting or excluding additional protein
complexes after
◦ Histone methylation
◦ Histone acetylation
◦ Others : phosphorylation, ubiquitinylation,
sumoylation, ….

11, 2015)
11, 2015)
11, 2015)
http://porpax.bio.miami.edu/~cmallery/150/gene/c7.19.4.histone.mod.jpg
http://www.nature.com/nsmb/journal/v14/n11/images/nsmb1337-F1.gif
11, 2015)
Li e. al.
Epigenetics - Biochemistry (Juny (2007) Cell
11, 2015) 128, 707
 < 2% of the total genomic sequence encodes
for proteins
 At least 90% of the genome is actively
transcribed into ncRNA
 The first ncRNA described : H19 role in
imprinting
 Two groups :
◦ Small ncRNA <200nt : mi RNA
◦ Long ncRNA or lncRNA – size ranges from 200 to
100kb

11, 2015)
 Small non coding db strands RNA
 19-22 nucleotides
 Around 2000 miRNA (MiR database)
 Repress expression of complementary mRNA
 Modulate expression of about 30% of the
genes
 1 miRNA can target about 100 mRNA
 Very resistant (as compared to mRNA)

11, 2015)
 DNA methylation and histone modification
regulate the expression of miRNAs, such as
let-7a, miR-9, miR-34a, miR-124, miR-137,
miR-148 and miR-203.
 Another subset of miRNAs controls the
expression of
◦ DNA methyltransferases,
◦ Histone deacetylases
◦ Polycomb group genes.

11, 2015)
11, 2015)
11, 2015)
11, 2015)
11, 2015)

Kati Sriwiyati MBK 155010070: Epigenetics - Biochemistry (Juny 11, 2015)

Hochgeladen von

Dokumentinformationen

Originaltitel

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Kati Sriwiyati MBK 155010070: Epigenetics - Biochemistry (Juny 11, 2015)

Hochgeladen von

Copyright:

Verfügbare Formate

Kati Sriwiyati

Epigenetics - Biochemistry (Juny 11, 2015)

Epigenetics - Biochemistry (Juny 11, 2015)

 While epigenetics often refers to the study of

Epigenetics - Biochemistry (Juny

Epigenetics - Biochemistry (Juny

Epigenetics - Biochemistry (Juny 11, 2015)

Epigenetics - Biochemistry (Juny

Methyl-CpG Histone deacetylase

Epigenetics - Biochemistry (Juny

Epigenetics - Biochemistry (Juny

Epigenetics - Biochemistry (Juny

Epigenetics - Biochemistry (Juny

Epigenetics - Biochemistry (Juny

Epigenetics - Biochemistry (Juny

Das könnte Ihnen auch gefallen