Transcription 3 Flashcards
How is the barrel shaped core histone octamer made?
- Two H3/H4 dimers form.2. These form a tetramer. 3. Two H2A/H2B dimers form and bind to the tetramer.
This is a predefined order of assembly.
What is the Nucleosome Core Particle (NCP)?
A histone octamer with DNA wrapped around it.
How many base pairs of DNA interact with a histone octamer?
146bp
How do histones interact with DNA?
Histones are cationic (lots of Lys/Arg) so bind to the negatively charged DNA backbone. Histones select the regions of DNA that are easiest to bend. Histones bind to the minor groove of DNA.
What is the chromatosome?
A nucleosome with the H1 linker histone bound, fixing the octamer to the DNA.
Why does nucleosome distribution vary between chromosomal loci?
Nucleosome binding is sequence dependent. Histone octamers can migrate to allow transcription.
What is a DNA solenoid?
Chromatin that has been condensed by zig-zag folding into a 30nm fibre. Helix consisting of 11nm nucleosome beads. Positively charged histone N termini extend from the nucleosome centre and bind to DNA on neighbouring nucleosomes.
How is the solenoid stabilised?
By H1 binding.
How much are sequential NCPs rotated in a solenoid?
By 71°.
What does the extent of solenoid compaction depend on?
Depends on the cellular environment. If transcription is needed the solenoid opens up.
How many nucleosomes are there per helical turn in a solenoid?
6
What regions of DNA do scaffold proteins bind to?
AT-rich regions.
How is the DNA scaffold further condensed?
By generating supercoils.
What does a chromosome consist of?
Helically packed loops of 30nm fibres
What is euchromatin?
Condensed chromatin that is transcriptionally active. Contains the largest proportion of genes in a chromosome. Not all transcribed at the same time, untranscribed regions may exist in the solenoid structure.
What is heterochromatin?
Condensed chromatin that is less transcriptionally active than euchromatin.
What is faculative chromatin?
Chromatin that can be changed from heterochromatin to euchromatin.
What is constitutive chromatin?
Chromatin that is condensed as heterochromatin throughout the cell cycle.
Describe the histone fold.
Long central alpha helix connected to 2 shorter terminal helices. Forms a stable X shaped structure when dimerised.
Approximately how many turns of DNA are there around each nucleosome?
1.7 turns
How is DNA wrapped around a nucleosome?
Tightly wrapped. DNA remains on the outside of the nucleosome disc like structure. DNA strands lie in parallel.
Why can’t transcription factors bind when DNA is wrapped tightly around nucleosomes?
Tight wrapping causes distortion of grooves and loss of shape complementarity.
What is the role of the linker histones?
Stabilise interactions between nucleosomes in compacted chromatin.
What does the H1 linker histone do?
Connects the entry and exit points of DNA on each nucleosome. Optimises the angle of each histone so that they naturally line up to form a helix.
Where can histones be acetylated?
On conserved lysines in the N termini of H3 and H4.
How does histone acetylation regulate transcription?
When acetylated histones become neutral and chromatin opens, allowing transcription factor binding.
What are the enzymes that control acetylation of histones?
Histone acetyltransferase and Histone deacetylase.
How can some gene specific transcription factors to bind in compact chromatin?
Can recognise the target sequence in compact chromatin, recruit HATs to open chromatin and activate transcription.
How can methylation of CpG islands prevent transcription?
Methyl-CpG binding protein binds and recruits HDAC to condense the chromatin.
