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Chromatin & Histone Structure Flashcards

1
Q

Define what chromatin is

A

The chromosomes and the associated proteins

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2
Q

What are histones?

A

The proteins the DNA winds around

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3
Q

What do the 4 levels of DNA packaging consist of?

A

1 - Nucleosomes = DNA + Histones
2 - 30nm fibres
3 - 80 - 100nm fibres
4 - mitotic chromosomes

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4
Q

What do chromosomes consist of?

A

DNA
Histone proteins
Non histone proteins
Non coding RNA

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5
Q

How is DNA packaged in interphase?

A

As nucleosomes

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6
Q

Why is DNA so compact?

A

Lots of DNA is tightly packed in higher order structures around the histone core

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7
Q

What is meant by higher order DNA structure?

A

The 4 levels of DNA packaging

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8
Q

When extracted at physiological salt concentration, how is the chromatin arranged?

A

As 30nm thick fibre

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9
Q

What is needed for higher order structures to form?

A
  • Linker histones
  • Histone tail interaction with adjacent nucleosomes
  • Binding of packaging proteins to histone tails
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10
Q

Why is the chromatin structure not static?

A

Nucleosomes have to be removed from DNA in front of the polymerase and replaced behind the polymerase, during Replication / Transcription

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11
Q

What are histone remodelling factors?

A

Enzymes that remove and replace nucleosomes

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12
Q

List the features of facultative heterochromatin

A
  • contains non expressive genes of that cell type
  • DNA tightly packaged as heterochromatin
  • Can be packaged as euchromatin in other cell types
    (expressed)
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13
Q

How is facultative heterochromatin regulated?

A

By chemical modifications of lysine residues in histone tails

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14
Q

Give examples of lysine modifications that can occur

A
  • methylation

- acetylation

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15
Q

What ensures the DNA histone complex doesn’t fall

apart?

A

Chromosomes are treated to extract histones and most non histone proteins. They appear as DNA loops attached to scaffold (tightly bound proteins)

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16
Q

Which method can be used to investigate chromatin structure?

A

DNase digestion

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17
Q

How does DNAse digestion work?

A

DNAse I cuts double stranded DNA

Histone binding protects DNA from digestion

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18
Q

Where on the DNA does the DNAse work?

A

On DNAse I sensitive sites (HSS)

19
Q

What DNAse I sensitive sites (HSS) are there on DNA?

A
  • Histone free DNA sequence
  • Naked DNA/ binding transcription factors
  • Promoters/ enhancers
20
Q

How do transcription proteins still access the DNA strand

despite its highly packaged structure?

A

TFs open up the chromatin structures, recruit basal TFs to enable transcription to occur

21
Q

How do Transcription factors regulate transcription?

A
  1. TFs bind to promoter (and enhancer)
  2. Recruit general basal transcription factors
  3. Assemble initiation complexes
  4. Recruits RNA polymerase
22
Q

How do TFs recruit chromatin modifying enzymes?

A

Via nulceur co - activator (NCoA)

or nucleur co - repressor (NCoR)

23
Q

What modifications do chromatin modifying enzymes carry out?

A

Acetylation

24
Q

Is acetylation of chromatin more prevalent in euchromatin

or heterochromatin?

A

Many Lysine residues in Euchromatin histones are acetylated

Heterochromatin histones are largely unacetylated

25
What is the role of Histone Acetyl Transeferases (HAT)?
- acetylate lysine residues on histones | - lead to unpacking of chromatin
26
What is the job of (HDACs) Histone deacetylases?
Deacetylate histones leading to compaction of chromatin
27
Where are thyroid hormones produced in the body?
Thyroid glands
28
What allows the hormones to bind to Thyroid hormone receptors (THRs)?
Hormones are very hydrophilic so pass through membrane and bind to their receptors
29
What is the role of the DNA Binding Domain on the THR (Thyroid Hormone Receptor)?
Binds specific Thyroid response element (TRE) | - acts as a regulatory TF
30
What happens in the absence of the thyroid hormone?
NCoR binds to HDAC and DNA methylated causes repression of genes chromatin packed tightly
31
What are the 3 domains on a Thyroid Hormone Receptor?
- Activation Domain - DNA binding Domain - Ligand Binding Dimerisation Domain
32
What is the significance of thyroid hormones?
Have major effects on metabolism
33
What is the significance of the TRE (thyroid response element)?
TRE binds a thyroid receptor protein dependent on the presence of the hormone
34
What occurs when thyroid hormone is available?
Hormone binds to thyroid receptor Undergoes conformational change Allowing NCoA to bind and recruit HAT and HMT Chromatin opens up to be transcribed
35
What does the Ligand Binding Dimerisation Domain do?
Binds the thyroid hormone
36
What are HMTs and what is their role?
Histone Methyl Transferases | - methylate histone tails
37
Describe and explain what HDMs are and their role
Histone Demethylases | - demethylate histones
38
How many times can a lysine residue be methylated?
Lysine residue can be mono, di, or tri- methylated
39
What effect does methylating lysine residues have?
Dependent on the residue it can either cause - chromatin condensation (H3K9me3) - chromatin decondensation (H3k9me1)
40
What is the histone code?
The hypothesis that the transcription DNA is partly regulated by the modifications to histone proteins, especially on their unstructured ends.
41
Which code reading proteins are domains found by?
Related domains are found in multiple code reading proteins e. g. - bromodomain bind to acetylated lysines - chromo/ tudordomain bind to methylated lysines
42
How is the histone code read?
By binding proteins
43
Are histone marks read singularly?
They're not read in isolation | there are multiple lysine residues on each histone with multiple histone modifications

FLC (34 decks)

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