chromatin structure and histone code Flashcards
What is the first level of DNA packaging? [2 marks]
- DNA is packed into nucleosomes (associated with histones).
- This increases DNA packaging by 7 fold.
What is the second level of DNA packaging? [2 marks]
- Nucleosomes pack themselves into 30nm long fibres.
- This increases packaging by 6 fold.
What is the third level of DNA packaging? [2 marks]
- 30nm fibres pack themselves into 80-100nm fibres.
- This increases packaging by 3 fold.
What is the fourth level of DNA packaging? [2 marks]
- This represented by the chromosome.
- This represents 10,000 fold packaging.
What are chromosomes made out of? [4 marks]
- DNA
- Histone proteins
- Non-histone proteins
- Non coding RNA
What is the structure of nucleosomes? [4 marks]
- Made up of 8 globular proteins. (“beads on a string”)
- Linker DNA outside
- DNA is wrapped around the outside of histones
- N terminal tails on the outside of the octamer core (positive charge)
What are the histones preset in nucleosomes? [4 marks]
- 2 x H2A
- 2 x H2B
- 2 x H3
- 2 x H4
Is DNA packed in the 3rd level functional or not? [1 mark]
NO
What does the compaction of nucleosomes require? [2 marks]
- Linker histones
- Modification of histones
Do nucleosomes need to be removed during transcription? [1 mark]
YES
What are histone remodelling factors? [1 mark]
Enzymes that remove and replace nucleosomes.
What does heterochromatin rich DNA look like? [3 marks]
- Dark when stained with Giemsa
- Gene poor
- Highly condensed (resistant to gene expression)
What does euchromatin rich DNA look like? [3 marks]
- Light when stained with Giemsa
- Gene rich
- Loosely condensed
What perecentage of the genome does heterochromatin rich genes make up and where are they found? [2 marks]
- ~10%
- Found near centromeres and telomeres
What perecentage of the genome does euchromatin rich genes make up and where are they found? [2 marks]
- ~90%
- Found in active genes
Where can facultative heterochromatin be found? [2 marks]
GLOBIN GENE
- present as euchromatin in reticulocytes.
- present as heterochromatin everywhere else.
What are ways to determine how nucleosomes are packed? [2 marks]
- Acetylation of lysine residues in histone tails.
- Methylation of lysine and arginine residues.
How do scaffolds protect DNA? [2 marks]
- They have insulators that insulate chromatin in one loop from the next.
- This prevents one set of genes from affecting another.
What are DNAse I sensitive sites (HSS)? [2 marks]
- Places that are easily digested by DNAse I, even in chromatin form.
- Have a regulatory role; allow regulatory factors to get to them.
What do transcription factors do to chromatin and how? [4 marks]
- They recruit chromatin modifying enzymes.
- This is via a nuclear coactivator (NCoA) or corepressor (NCoR).
- NCoA bind a bunch of enzymes (histone acetyl transferase and histone methyl transferase).
- This opens up the chromatin structure.
How does acetylating histones work? [2 marks]
- Acetylated HAT acetylate amino group of lysine.
- Lysine loses its positive charge.
Acetylation in heterochromatin and euchromatin [2 marks]
HETERO: unacetylated
EU: acetylated
What happens to the thyroid hormone receptor without thyroid hormone? [2 marks]
- Thyroid hormone receptor binds NCoR which binds histone deacetylase (HDAC) and DNA Methylase.
- Chromatin is packed tightly.
What happens to the thyroid hormone receptor in the presence of the thyroid hormone? [3 marks]
- When hormone binds to its receptor, there’s a change in confirmation.
- Receptor binds NCoA which recruits HAT and HMT.
- Histones are modified and chromatin is opened up.
How can lysine be methylated? [3 marks]
- Monomethylated
- Dimethylated
- Trimethylated
How are histone modifications read? [2 marks]
- By binding proteins
- Read multiple lysine residues and multiple modifications.
What is the clinical significance of HDAC? [3 marks]
- HDAC inhibitors are used to activate genes.
- They keep them in an open configuration.
- HDAC affects gamma globin gene in sickle cell anaemia or cancers.
