chromatin structure and function Flashcards
what is a chromatin
it is a nuclear complex of DNA and proteins to form chromosomes found in the nucleus of eukaryotic cells
what are the functions of chromatin
packaging of long DNA molecules into a denser and more compact shape to fit into the nucleus.
for the protection of the DNA structure and sequence.
what are the 4 levels of DNA packaging
nucleosome- beads on a string
30nm fibre
active chromosome
metaphase chromosome
When does chromatin start to condense
during prophase and it becomes visible as chromosomes.
during interphase what is chromatin organised as
euchromatin and heterochromatin
describe the 1st level of DNA packaging
-DNA+histones (nucleosomes) which are made up of double-stranded DNA wrapped around histone proteins.
-increases DNA packaging by 7 fold
-it has approximately 10nm diameter
describe the 2nd level of DNA packaging
-nucleosomes pack themselves into fiber
-increases DNA packaging by 7 fold
-it has a diameter of 30nm
describe the 3rd level of DNA packaging
-fibers pack themselves into loops and topologically associated domains(TADs) and form chromatin
-increases DNA packaging 3 fold
-has a diameter of 100-250nm
describe the 4th level
-it is represented by mitotic chromosomes(only visible during cell division)
-increases DNA packaging by 1000 fold
-it has a diameter of 700-1000nm
describe euchromatin
-it is rich in genes.
-has lightly staining areas of chromatin.
-it is accessible to proteins involved in DNA replication and repair and transcription.
-low compacticity chromatin; 10nm fiber “beads in a string”.
describe heterochromatin
-highly condensed; 30nm fiber
-gene poor
-it has darkly staining areas of chromatin
-it can be facultative or constitutive.
describe constitutive heterochromatin
these are heterochromatin containing highly repetitive sequences of DNA that are genetically inactive and serve as a structural element of a chromosome.
describe facultative heterochromatin
this refers to regions of a chromosome that may be uncondensed(become euchromatin) at certain moments of their development. they contain genes that are silenced through different mechanism and these genes can only be expressed at certain moments of person’s life.e.g inactivation of the chromosome X in female mammals
describe how chromatin shows elasticity
it can condense and decondense which is enabled by a choice of histone variants, modifications of DNA bases and reversible post-translational modifications (PTM) of histone tails.
What are function of TADs
these are highly conserved chromatin domains that shape functional chromosomal associations. their disruption leads to diseases.
what are chromosome territories
these are non-overlaping seements of the nucleus that contain uncondensed chromosomes they are composed of TADs.
what do histones assemble to form?
an octamer core which is composed of H3H4 tetramer which is flanked by H2A and H2B dimers. it also contains n-terminals which stay outside the octamer core.
how many base pairs of DNA wrap around a histone core
146 bp which is 1.7turns of DNA.
what is the function of H1 protein
H1 protein acts like a clip that keeps the DNA wrapped around the histone core in place.
what is a linker DNA
this is a DNA strand(38-53bp) that links adjacent nucleosomes.it helps to stabilize the zig-zagged 30nm fiber
what is the protein loop that binds to DNA and facilitates the formation of loops
cohesin
what is epigenetics
these are reversible changes in gene expression that do not involve any changes in DNA sequence. it occurs as a result of environmental factors or external factors or as part of development program
what are the 4 types of histone modifications
histone methylation
histone acetylation
histone phosphorylation
histone ubiquitylation
features of histone methylation
-histone tails are methylated by histone methyl transferases and demethylated by histone demethylases.
-it can either be mono, di or tri methylation of lysines and arginines
-the methylation of some lysine residues can cause condensation (e.g H3K9me3) while some can lead to decondensation (e.gH3K9me1)
features of histone acetylation
- histone tails are acetylated by histone acetyl tranferases and deacetylated by histone deacetylases.
-most common is the acetylation of lysines.
-acetylated histones are usually associated with relaxed chromatin and gene expression while deacetylated histones are usually associated with closed chromatin and gene silencing.
-aberrant acetylation is usually associated with tumors and hematological malignancies
what are features of histone phosphorylation
-histone tails are phosphorylated by protein kinases and dephosphorylated by proteases.
-it can occur on serine, threonine and tyrosine residues
-Phosphorylation of H3S10 and H3S28 is
involved in chromatin condensation during
mitosis and meiosis, as well as in chromatin
relaxation linked to transcription activation.
what are features of protein ubiquitylation
-histone tails are ubiquitinated by ligases and deubiquitinated by deubiquitinating enzymes
-usually occurs on lysines of H2A and H2B histones.
-H2Aub is associated with gene silencing while H2Bub is associated with transcription activation.
what is the histone code
this is the combination of post-translational modifications on the same histone tails.
what are code readers
protein complexes that
read combinations of marks:
chromodomains specifically recognize
methylated residues, while
bromodomains bind acetylated
residues. This read leads to chromatin
remodelling (open or close).