lecture 4- chromosomes Flashcards
what is the largest micromolecule in the cell
chromosomes
which chromosome is the smallest
21
(1-22)
describe the chromosomes of viruses
can be circular or linear and can be single or double stranded (DNA viruses)
describe the chromosomes of bacteria
only circular chromosomes
describe chromosomes in eukaryotic cells
chromosomes inside nucleus, nuclear membrane separating from other organelles
DNA in mitochondria = ___
circular
describe DNA supercoiling
- the first level of compaction of DNA in bacteria (coiled coil)
- DNA double helix coiled on itself- forms a new superhelix, called a supercoil
- add 2 turns — over-rotate— positive supercoil
- remove 2 turns — under-rotate — negative supercoil
DNA unwinding and relaxation are catalyzed by ___
DNA topoisomerases
describe the packaging of bacterial chromosomes
- DNA gyrase (a type II topoisomerase) introduces negative supercoils to bacterial chromosomes
- nucleoid: region in bacteria where chromosomes are arranged (not separated from other organelles, but localized)
- a “typical” bacterial chromosomes contains about 50 giant loops of supercoiled DNA arranged around a protein scaffold (proteins in scaffold are positively charged because DNA is negative)
describe eukaryotic chromosome compaction
- length of each chromosome may be more than 2000 times the size of nucleus
- chromatin: made of 50% DNA and 50% proteins
. basic unit of chromatin is nucleosome
. nucleosomes= the basic units of DNA condensation (beads on a string,
nucleosomes made of DNA and histones) - next level of compaction is the 30 nm chromatin fibre of packaged nucleosomes
- chromosomes are in most condensed form and duplicated right before cell division
when they isolated proteins bound to DNA and run on a gel, they found…
4 histone proteins in equimolar amounts- H2A, H2B, H3, H4 (also found H1 but in smaller amounts)
- small, highly conserved positively charged proteins
- about 25% of each histone is made of lysine and arginine
describe histone protein structure
- all have N terminal tails that are important for the regulation of chromatin structure
- histone-fold domain has 3 alpha helices
- N terminal tails are unstructured domains
- C terminus
Histone fold motif (domain): 3 alpha helices — supersecondary structure
histone octamers organize _____
DNA into repeating units
describe the histone proteins when DNA is not present and is present
not present: H2A & H2B form a dimer ; H3 & H4 form a tetramer
DNA present: they come together and form a histone octamer
describe histone octamers
- core of nucleosome formed by two of each core histone: H2A, H2B, H3, H4
- left-handed supercoil of 146 bp winds 1.67 times around the histone octamer (compacts DNA 6-7x)
- N terminus tails of histone stretch out of nucleosome
- histone folds are responsible for protein-protein interactions between core histones as well as binding DNA to form nucleosomes
interactions of DNA and histones are through ___
hydrogen bonds
name 2 ways to regulate chromosome structure
1- chromatin remodeling complexes
2- histone modifications by enzymes
describe chromatin remodeling complexes
nucleosomes can be rearranged by ATP-driven chromatin remodeling complexes
- these complexes change the association between the histone cores with the DNA wrapped around
- the most well-known chromatin remodeling complex is SWI/SNF in humans
name 3 examples of how variant histone subunits locally alter chromatin structure and function
1- replacing H3 with H3.3 — maintains a transcriptionally active open state
2- replacing H3 with CENPA — maintains kinetochore attachment to spindle fibers
3- replacing H2A with H2AX — H2AX is phosphorylated and attracts DNA repair proteins to seal DNA Break
describe histone modifying enzymes
modifications of histone tails alter chromatin structure
- histone modifying enzymes attach chemical groups to amino acids of nucleosome subunits
- if the outcome is the direct result of a modification — cis
- if the modification attracts another protein that performs the histone-modifying function — trans
- the modifications to tails with either affect clamping together nucleosomes closer or pushing them farther away, altering DNA accessibility
name a few examples of histone tail modifications
- acetylation of histone tails in lysine residues decreases positivity and enhances DNA accessibility (because looser)- acetylation done by enzymes called HAT- histone acetyltransferase
- tails comprise 25-30% of the mass of histones, tails are rich in:
lysine: acetylation, methylation, ubiquitination
serine: phosphorylation
arginine: methylation
can histone tail modifications be passed down?
yes, histone modifications are inheritable
- inheritance of genetic properties that are not coded in DNA sequence = epigentic
describe H1
H1 is the “linker histone,” packs adjacent nucleosomes
- H1 helps nucleosomes condense into a higher level of packaging – 30 nm filament
- the 30 nm fiber is maintained by interactions between tails of the adjacent nucleosomes as well as compaction by H1
euchromatin vs. heterochromatin
eu- undergoes condensation and decondensation- becomes active (relaxed and accessible)
hetero- stays more condensed
