Chromosomes, Chromatin, and the Nucleosome
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Chromosomes, Chromatin, and the Nucleosome
Chromosomes: DNA associated with proteins
1. The chromosome is a compact form of the DNA that readily fits inside the cell.
2. Packaging the DNA into chromosomes serves to protect the DNA from damage.
3. Only DNA packaged into a chromosome can be transmitted efficient to daughter cells.
Table I: variation in chromosome makeup in different organisms
The traditional view is that prokaryotic cells have a single, circular chromosome,and eukaryotic cells have multiple, linear chromosomes.
Table 2. Comparison of the gene density in different organisms’
genomes
Comparison of the chromosomal gene density for different organisms
65kb region
The organization and content of the human genome
Pseudogenes arise from the action of an enzyme called reverse transcriptase
(dinucleotide repeats)
( greater 100bp, mostly transposable element)
The majority of human intergenic sequences areComposed of repetitive DNA
Table 7-3
Contribution of introns and repeated sequences to different genomes
introns (p. 135)
Chromosome duplication and segregation
Eukaryotic chromosomes require Centromeres, Telomeres, and Original of Replication to be maintained during cell division
More or less than one centromere leads to chromosome loss or breakage
Centromere size and composition varies dramatically
Telomeres
1. Telomeres are bound by a number of proteins. These proteins distinguish the natural ends of the chromosome form sites of chromosome breakage and other DNA breaks in the cell. DNA ends are the sites of frequent recombination and DNA degradation. The Proteins at telomeres form a structure that is resistant to both events.2. Telomeres act as a specialized origin of replication that allows the cell to replicate the ends of the chromosomes.
The eukaryotic mitotic cell cycle
Each chromosome of the duplicated pair is called a chromatid, the two chromatids of a given pair are called sister chromatids.
The events of mitosis
Changes in chromatin structure-DNA condensation and decondensation
Chromosomes are maximally condensed in M phase
• Sister Chromatid cohension and Chromosome condensation are mediated by SMC ((structural maintenance of
chromosome) proteins
Models for the structure of cohesins and condensins
The structural of cohesin is a large ring composed of two SMC proteins and a third non-SMC protein. SMC (structural maintenance of chromosome) proteins
Mitosis maintains the parental chromosome Number
Meiosis reduces the parental chromosome number
Formation of chiasma
Homologous recombination
cohesion is lost
Formation of chromatin structure
nucleosome- building blocks of chromosomes
H2A: redH2B: yellowH3: purpleH4: green
Histones are small, positively-charged proteins
The assembly of a nucleosome
The N-terminal tails are accessible to protease trypsin (specifically cleaves protein positively-charged amino acids)
The nucleosome has an approximate twofold axis of symmetry
Interactions of the histones with nucleosomal DNA
H3.H4 tertramer H2A.H2B dimer
central 60bp region and two ends
Each associate with about 30 bp of DNA on either side of the central 60 bp
Histones contact the minor groove of the DNA by forming a large number of hydrogen bonds
The large number of the hydrogen bonds provide the driving force to bend the DNA
Higher-order chromatin structure
H binds to linker DNA at one end ofThe nucleosome and the central DNA helix
The addition of H1 leads to more compact nucleosomal DNA
Without H1
Histone H1 induces tighter DNA wrapping around the nucleosome
30-nm fiber
Superhelix, 6 nucleosome per turn, supported by EM and X-ray studies
Based on zigzag pattern upon H1 addition, requires linker DNA to pass through central axis,
The core Histone N-terminal tails are required for the formation of the 30-nm fiber
The tail of H2A, H3 and H4 interact with adjacent nucleosome
Higher compaction of DNA involves large loops ofnucleosomal DNA
Nuclear scaffold (Topo II, SMC)
Histone variants alter nucleosome function1. H2A.z histone inhibits nucleosome from forming repressive chromatin structures, creating regions of easily accessible chromatin that are more compatible with transcription
2. CENP-A replace H3, is associated with nucleosomes that include centromeric DNA
Regulation of chromatin structureThe interaction of DNA with histone octamer is dynamic
Unwrapping of the DNA from nucleosome is responsible for the accessibility of the DNA
Nucleosome movement by nucleosome remodeling complexes
restructure
ATP-dependent chromatin remodeling complex
SWI/SNF 8-11 subunits Bromodomain
ISWI 2-4 subunits No
Mi2/NuRD 8-10 subunits chromodomain
Nucleosome Positioning by DNA-binding proteins
exclusion
Nucleosome Positioning by DNA-binding proteins
Inducing assembly
Modifications of the histone N-terminal tails alters the function of chromatin
Acetylation: transcription activation
Effects of histone tail modification
Nucleosome modifying enzymes
Chromatin remodeling complex and histone modifying enzymes work together to alter chromatin structure
Nucleosome AssemblyThe inheritance of histones after DNA replication The old histones are present on both of the daughter chromosome
H3.H4 tetramers remain bound to one of the two daughter duplexe at random but H2A.H2B dimers are released and enter the local pool for new nucleosome assembly.
Inheritance of parental H3.H4 tetramers facilitate the inheritance of chromatinstate
Nucleosome Assembly
The assembly of nucleosomes is not a spontaneous process, it requires high salt condition in-vitro.
Proteins required to direct the assembly of histones to DNA are histone chaperones.
Name histones bound
CAF-1 H3. H4
RCAF H3. H4
NAP-1 H2A.H2B
(negatively-charged protein)
How histones chaperones facilitate the assembly of nucleosomeduring DNA replication
(sliding clamp)
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