Chromatin Structure + Histone Code Flashcards
What is chromatin?
Chromosomes + associated proteins
What is nucleosome?
DNA + histones
Histones are responsible for …….. of packaging
1st level
Nucleosome structure increases DNA packaging in 1st level of packaging by…..
7 fold
2nd level of packaging
Nucleosomes pack themselves in fibres of 30nm constituting 2nd level of packaging
Increases packaging 6 fold
3rd level of packaging
30nm fibres pack themselves into 80-100 fibres constituting to 3rd level of packaging
Increases packaging 3- fold
4th level of packaging
Is represented by mitotic chromosome
Represents 10000 fold packaging
Chromosomes consist predominantly of
DNA
Histone proteins
Non-histone proteins
Non-coding RNA
Histone assemble to form an octamer core
2 molecules of each histone: H2A,H2B, H3& H4
N-terminal tails outside octamer core=> there is an electrostatic attraction between negatively charged DNA backbone + positive N terminal tail
Compaction of nucleosomes to form higher order structures involves
Linker histones
Interaction of histone tails with adjacent nucleosomes
Binding of packing proteins to histone tails
What are histone remodelling factors?
Enzymes that remove + replace nucleosomes
What is euchromatin?
Lightly staining areas of chromatin
Rich in genes
Made up of nucleosomes but not dense higher order packaging
What is heterochromatin?
Darkly staining areas of chromatin
Few genes
Dense higher order packaging of nucleosomes
What is facultative heterochromatin?
Contains genes not expressed in that cell type
DNA tightly packaged as heterochromatin
But may be packaged as euchromatin in other cell types
What determines whether nucleosomes are packed as euchromatin or heterochromatin?
One key of control- chemical modification of lysine residues in histone tails
Acetylation
Methylation
What are DNAase I sensitive sites?
Sequences of DNA without histones
May be naked or binding transcription factors
Cut by very brief digestion with DNAase I
Found in promoters + enhancers
If DNA is tightly packaged in higher order chromatin structure, how can all these proteins get at DNA?
They can’t do until you start to unwind chromatin
First TF opens up chromatin structure
Then recruits basal TFs
Transcription occurs
Give examples of chromatin modifying enzymes
HAT (histone acetyltransferase)
HMT (histone methyltransferase)
Histone modification- acetylation
Amino group is positively charged
When it is acetylated, HAT takes acetyl group from acetyl coA + attaches it to amino group
This leads to loss of positive charge
What does HAT do?
Acetylate lysine residues on histones, leads to unpacking of chromatin
What does HDAC do?
De-acetylate histones, lead to compaction of chromatin
What does HMT do?
It methylates histone tails
What does histone demethylases (HMD) do?
Demethylate histone tails
What does methylation of lysine residues cause?
Methylation of some lysine residues causes chromatin condensation
Methylation of other lysine residues causes chromatin decondensation
