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Gregor Mendel (1823-1884). DNA (gene). Transcription. RNA processing (splicing etc). mRNA. Translation. Folding. Post translational modifications. Protein. Proteolysis. Peptides/amino acids. William Bateson (1861-1926) coined the name “genetics” in 1909.

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slide2

DNA (gene)

Transcription

RNA processing (splicing etc)

mRNA

Translation

Folding

Post translational modifications

Protein

Proteolysis

Peptides/amino acids

genetics is the study of genes
Genetics is the study of genes

Whether geneticists study at the molecular, cellular, organismal, familial, population, or evolutionary level, genes are always central to their studies.

topics studied in the department of genetics
Topics studied in the department of Genetics
  • Telomeres of chromosomes
  • Cell cycle
  • Nuclear architecture
  • Population genetics
  • Genetics of tomatoes
  • Quantitative traits of milk production in cows
  • Chromosome X inactivation
  • RNA splicing
  • Yeast meiosis
  • Genetics of the CF disease
  • Chromosomal fragile sites
  • Human stem cells
  • Oncogenes
how many genes do we have31
How many genes do we have ?

The answer to this question is almost meaningless because:

how many genes do we have32
How many genes do we have ?

The answer to this question is almost meaningless because:

  • Each gene can give rise to several proteins by alternative splicing
how many genes do we have33
How many genes do we have ?

The answer to this question is almost meaningless because:

  • Each gene can give rise to several proteins by alternative splicing
  • And each protein can be modified in multiple ways by phosphorylation, methylation, acetylation, glycosylation etc.
how many genes do we have34
How many genes do we have ?

The answer to this question is almost meaningless because:

  • Each gene can give rise to several proteins by alternative splicing
  • And each protein can be modified in multiple ways by phosphorylation, methylation, acetylation, glycosylation etc.
  • These modified proteins can further take part in different protein complexes.
slide36
DNA is packed together with histones and other proteins into chromatin.
  • Chromatin is a highly dynamic material which carries a substantial amount of epigentic information.
  • All cells in the organism carry the same genetic material, however each cell type expresses different genes.
epigenetics
Epigenetics
  • Epigenetics - Heritable changes in gene expression that operate outside of changes in DNA itself
chromatin remodeling
Chromatin remodeling
  • Protein expression can be induced and repressed over many orders of magnitude. An important part of this regulation is exerted via chromatin remodeling by DNA methylation and numerous modifications mainly of the N-termini of histones - acetylation, methylation, phosphorylation and ubiquitilation.
epigenetic chromatin regulation
Epigenetic chromatin regulation

A. Modification at the DNA level

1. cytosine methylation

B. Histone modification - the histone code

1. Histone acetylation

2. Histone methylation

3. Histone phosphorylation

4. Histone ubiquitilation

5. Different types of histones

cpg dinocleotides are palindromic
CpG dinocleotides are palindromic

5’ CpG 3’

3’ GpC 5’

cpg dinocleotides are palindromic43
CpG dinocleotides are palindromic

5’ CpG 3’

3’ GpC 5’

slide46

DNA demethylation of early embryos

3h

6h

8h

Aphidicolin

First met.

P

P

P

M

M

M

P

M

22h 2 cells

45h 4 cells

establishment of dna methylation pattern
Establishment of DNA methylation pattern
  • The methylation pattern of the genome is established anew every generation. In that sense methylation is an epigentic phenomenon - it influences the genetic material but it is not inherited from one generation to another.
  • All methylation (or at least almost all) is erased during early embryogenesis and reestablished
genomic imprinting

Genomic imprinting

Some genes are expressed only from the maternal genome and some only from the paternal genome

genomic imprinting49

Genomic imprinting

Some genes are expressed only from the maternal genome and some only from the paternal genome

It is estimated that about 40 genes are imprinted and they can be found on several different chromosomes

genomic imprinting50

Genomic imprinting

Some genes are expressed only from the maternal genome and some only from the paternal genome

It is estimated that about 40 genes are imprinted and they can be found on several different chromosomes

For example - igf2, h19, igf2r and genes involved in the Angelman and Prader Willi syndromes

slide53

Control (P+M)

Maternal

Paternal

roles of dna methylation
Roles of DNA methylation
  • Transcriptional silencing
  • Protecting the genome from transposition
  • Genomic imprinting
  • X inactivation
  • Tissue specific gene expression
epigenetic chromatin regulation56
Epigenetic chromatin regulation

A. Modification at the DNA level

1. cytosine methylation

B. Histone modification - the histone code

1. Histone acetylation

2. Histone methylation

3. Histone phosphorylation

4. Histone ubiquitilation

5. Different types of histones

role of histone acetylation
Role of histone acetylation
  • Acetylated histones open up the chromatin and enable transcription. Histones are acetylated by HAT (histone acetylases) which are parts of many chromatin remodeling and transcription complexes.
role of histone de acetylation
Role of histone de-acetylation
  • Deacetylated histones are tightly packed and less accessible to transcription factors.
  • Histones are deacetylated by HDAC (histone de-acetylase) proteins.
histone phosphorylation h3
Histone phosphorylation (H3)
  • Histones are phosphorylated during mitosis.
  • Histones are also phosphorylated by signal transduction pathways like the ERK pathway in response to external signals. It is not known how (and if) this phosphorylation contributes to gene expression.
epigenetic chromatin regulation70
Epigenetic chromatin regulation

A. Modification at the DNA level

1. cytosine methylation

B. Histone modification - the histone code

1. Histone acetylation

2. Histone methylation

3. Histone phosphorylation

4. Histone ubiquitilation

5. Different types of histones

epigenetic chromatin regulation73
Epigenetic chromatin regulation

A. Modification at the DNA level

1. cytosine methylation

B. Histone modification - the histone code

1. Histone acetylation

2. Histone methylation

3. Histone phosphorylation

4. Histone ubiquitilation

5. Different types of histones