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In eukaryotes, the __ is more correlated with the complexity of the organism, not the __
number of genes; size of the genome
- The size of genome is very variable between different organisms.
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Genes are more __ in prokaryotes than eukaryotes. Roughly, there is a __ between the density of genes and the complexity of the organism.
dense; reverse correlation
Viruses have the highest gene density, followed by bacteria. In eukaryotes, large sequences of DNA allocated for the regulation of gene expression.
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intergenic sequences
does not code for structural or functional proteins or functional RNAs. make up 60% of the genome of humans (The other 40% are genes and gene related sequences.) 2 types: unique and repeated
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the areas of the genome that contribute in regulating expression of genes. also part of non-coding regions of DNA
- regulatory sequences
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Approximately 62% of the human genome comprises of __, which have no known function. These sequences used to be called junk DNA (but in fact they may have important functions)
intergenic regions (between genes)
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The bulk of intergenic DNA is made up of __ (half of human genome)
repeated sequences
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individual repeat units distributed around the genome
- interspersed repeats (genome wide repeats)
- 45% of genome
- (longer than tandem repeats)
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repeat units that are placed next to each other in an array
tandemly repeated DNA
- (Some of these tandem repeats are in the centromere and telomere - may have structural function - and also in other parts of the genome.)
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metaphase chromosomes: For the purpose of cell division, the DNA adopts a more __ form of packaging.
compact
(resulting in the highly condensed form that can be seen with the light microscope)
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The metaphase chromosomes form after __ has taken place, and so each contains __ copies held together at the __
- DNA replication;
- 2;
- centromere
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The arms of the chromosomes are called __ and have terminal structures called __
- chromatids (2 sister chromatids);
- telomeres
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Sister chromatids are kept attached to each other by __
cohesins
-
cohesin
- 2 large structural maintenance of chromosome proteins (SMC) with 2 non-SMC protein to form a ring (around the 2 sister chromatids)
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Digestion of non-SMC causes __
opening of the ring and separation of chromatids
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How does chromosome condensation happen?
Condensin (ring shaped SMC containing protein complexes) possibly cause condensation by linking different parts of a chromosome together
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By electron microscopy, chromatin can be seen in 2 forms during __ (non dividing cells and not condensed chromosome): __
- interphase;
- 30 nm fiber (main form, more common) & 10 nm fiber
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There is a contact between histones and every __ groove of the DNA around it. Interaction of histones with the groove is mostly in the form of __ bonds between __. These interactions are __ DNA sequence specific.
- minor;
- hydrogen;
- proteins and oxygen of the phosphodiester bonds in the backbone of DNA (also only some hydrogen bonds with bases);
- not
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reasons for DNA bending around histones
- many hydrogen bonds formed between DNA and histones
- the effect of positively charged amino acids of histone (basic) on the negative phosphates (acidic) of DNA
These basic amino acids also help to keep the twice turned of DNA next to each other on histones.
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DNA is bent on the __. It is easier to bend if __ sequences are in the minor groove (facing histones) and __ sequence in the minor grooves facing outward.
- Nucleosomes preferred to position according to this sequence but it is not a very restricted rule.
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__ stabilize the 30 nm fiber by interacting with the adjacent nucleosome
Amino tails of histones
Chemical modification of the tails probably affects the structure of the 30 nm fiber.
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During interphase, the __ fiber is the dominant structure of euchromatin
30nm
(There is also 10nm fibers)
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Packing of DNA to the 10 and 30nm fiber →
40 fold compaction of DNA length. Further compaction is needed
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Loops of 30nm fibers (with size 40-50kb) attach to the protein structures known as __
nuclear scaffold
- The nature of nuclear scaffold isn't clear but topoisomerase II and SMC proteins usually are isolated from the scaffold
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__ at the site of the DNA, the double strand break and is phosphorylated → signaling to the DNA repair system
H2A.X
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CENP-A
- the replacement of H3 in the centromere
- has an extended amino tail → interaction with kinetochore protein CENP-C
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In the amino tail:
- Lysines are modified with a single acetyl or become methylated.
- Arginines can be methylated.
- Serines & threonines are phosphorylated
- sometimes ADP-ribosylation
- somtimes ubiquitinated or sumolated
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histone acetyl-transferases (HATs)
enzymes that add acetyl groups to histones
- Histone acetylation is an integral part of transcription initiation.
- Adding acetyl will remove the + charge and make the chromatin less condensed
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Histone deacetylases (HDACs)
enzymes that remove acetyl groups from the histone tails
- Gene inactivation is partly the function of HDACs
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Proteins interacting with methylated histone are involved in __
- suppression of transcription and generation of heterochromatin
- makes chromatin more condensed
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Chromatin-remodeling and histone modifying complexes work together to __
alter chromatin structure
-
__ of __ will activate transcription & __ will suppress transcription
- Acetylation;
- lysines of H3 & H4;
- methylation
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Modification of histones generate binding sites for __. These interacting proteins recruit other proteins that __
- more of and other chromatin modifying enzymes;
- modify adjacent histones → maintenance and propagation of the modifications (e.g. HATs)
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Nucleosome remodeling complexes use ATP to:
- slide the histone octomer
- or eject the octomer out or transfer it to another double strand
- or replace H2A-H2B with other variants such as H2A.X-H2B
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After DNA replication, the 2 daughter DNA contain __ histones
new (made during DNA replication) & old
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H3-H4 histones are directly distributed in a random manner, so both daughter DNA receive __
part of the old histones at places similar to the old DNA. Also, the new H3-H4 histones assemble to both daughter DNAs
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Old H2A-H2Bs join to a pool containing __
the new H2A-H2Bs and then they assemble with the DNA attached H3-H4s
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Histone modification enzymes (e.g. HATs) are recruited by __
the old histones inherited by both DNAs
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Histone modification enzymes modify __
the neighboring nucleosomes → disseminating the histone modification pattern similar to what existed in the original before the replication
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