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Sister chromatids are kept attached to each other by __
cohesins
2 large structural maintenance of chromosome proteins (SMC) w/ 2 non-SMC proteins form a ring around the 2 sister chromatids
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How do chromatids separate?
Digestion of non-SMC opens the rings.
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How does chromosome condensation happen?
Condensin (ring-shaped SMC) contains protein complexes that possibly cause condensation by linking different parts of a chromosome together.
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Chromatin can be seen in 2 forms during __, as __ & __
- interphase (not dividing cells & not condensed chromosome);
- 30 nm fiber (main form, more common);
- 10 nm fiber
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Interaction between histones and DNA are __ to the DNA sequence
not specific
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There is a contact between histones and __ of the DNA around it in the form of __ bonds between __ of the histones and __ of __ bonds in the backbone of DNA
- every minor groove;
- hydrogen;
- amino acids;
- oxygen
- phosphodiester
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reasons for DNA bending around histones
- many hydrogen bonds formed between DNA & histones
- the effect of positively charged amino acids of the histones (basic) on the negatively charged phosphates (acidic) of DNA. The basic amino acids also help to keep the twice turned DNA next to each other on histones.
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DNA is bent on the __ (nucleosome position). It is easier to bend if __
- octamer;
- A:T sequences are in the minor groove facing histones & G:C sequences in the minor groove are facing outward
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__ stabilize the 30 nm fiber by __
- Amino tails of histones
- interacting with the adjacent nucleosome
Chemical modification of the tails probably affects the structure of the 30 nm fiber.
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Packing DNA to the 10 & 30nm fiber leads to a 40 fold compaction of DNA length, but __. So __ attach to the protein structures known as __
- further compaction is needed;
- Loops of 30 nm fibers;
- nuclear scaffold
The nature of nuclear scaffold is not clear, but topoisomerase II & SMC proteins usually are isolated from the scaffold.
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H2A.X
a histone variant. is at the site of DNA double strand break & is phosphorylated, which signals the DNA repair system
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CENP-A
a histone variant. the replacement of H3 in the centromere. has an extended amino tail & interacts with the kinetochore protein CENP-C
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In the amino tails of histones, lysines can be modified by __
a single acetyl or become methylated
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In the amino tails of histones, arginines can be modified by __
methylation
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In the amino tails of histones, serines & threonines can be modified by __
phosphorylation
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The amino acids of histones can also be modified by __
ADP ribosylation & ubiquination or sumolation
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HATs
- histone acetyl transferases
- enzymes that add acetyl groups to histone tails
- causes the histone amino acids to lose positive charge & lose attachment from DNA
- Histone acetylation is an integral part of transcription initiation
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HDACs
- histone deacetylases
- enzymes that remove the aceytl group from the histone tails
- Gene inactivation is partly the function.
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Proteins interacting with a methylated histone are involved in __
suppression of transcription & generation of heterochromatin (more compact chromatin)
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__ of histone tails initiates transcription.
__ of histone tails suppresses transcription.
__ of histone tails causes gene inactivation.
- Acetylation (adding acetyl groups) - HATs
- Methylation (adding methyl groups)
- Deacetylation (removing acetyl groups) - HDACs
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How is chromatin structure altered?
Chromatin-remodeling & histone-modifying complexes work together to alter chromatin structure. Sequence-specific DNA-binding proteins typically recruit these enzymes to specific regions of a chromosome.
The DNA-binding protein 1 (blue) first recruits a histone acetyltransferase that modifies the adjacent nucleosomes, increasing the accessibility of the associated DNA by locally converting the chromatin fiber from 30 nm to the more assessable 10 nm form.
This increased accessibility allows the binding of a 2nd DNA-binding protein (orange) that recruits a nucleosome-remodeling complex. Localization of the nucleosome-remodeling complex facilitates the sliding of the adjacent nucleosome, which allows the binding site for a 3rd DNA-binding complex (green) to be exposed.
ex. This could be the binding site for that TATA-binding protein at a start site of transcription
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histone modification & chromatin remodeling image
Acetylation of histone tails results in a less compacts chromatin structure. (lose positive charge so DNA becomes more loose and lose attachment from the histones)
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Histone modifications such as methylation or deacetylation may result in __
a more compactness of chromatin structure
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Nucleosome remodeling complexes may also have subunits that __
target them to specific sites. e.g. to nucleosomes with particular modifications on their amino histone tails
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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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histones during DNA replication
New histones are made, but the old histones are also distributed between the 2 daughter DNA
H3-H4 histones directly distribute in a random manner so both daughter DNA receive part of the old histones at similar places to the old DNA. New H3-H4 histones also assemble to both daughter DNAs
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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inheritance of patterns of histone modifications
Histone modification enzymes (e.g. HATs) are recruited by the old histones & inherited by both DNAs
These enzymes modify the neighboring nucleosomes, disseminating the histone modification pattern similar to what existed in the original nucleosomes before replication.
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