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· Although enormously long strings of nucleosome form on the __, chromatin in a living cell rarely adopts the __
o Instead, the nucleosomes are arranged how, generating regular arrays in which the DNA is even more __
· The structure of a __supports the __model for the stacking of nucleosomes in the 30-nm fiber
- chromosomal DNA
- extended “beads on a string” form
- packed on top of one another
- highly condensed
- tetranucleosome
- zigzag
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· What forms nucleosomes to stack of tightly on each other in a 30-nm fiber are the __ formed by __, most notably the __, as well as the additional __that is often present in a 1-to-1 ratio with __, known as __.
o This __ is larger than the individual core histones and it has been considerably less well conserved during evolution
- nucleosome to nucleosome linkages
- histone tail
- H4 tail
- histone
- nucleosome cores
- histone H1
- linker histone
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§ A single __ molecule binds to each __, contacting both __, and changing the path of the DNA as it exits from the __
· A change in the exit path in DNA seems crucial for __ so that it interlocks to form the 30-nm fiber
- histone H1
- nucleosome
- DNA and protein
- nucleosome
- compacting nucleosomal DNA
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· It is possible that the __ found in chromosomes is a __ of several different variations
o These differences in __ probably introduce __ into the structure; and, the presence of many other __, as well as proteins that bind directly to histones, will add important additional features to any array of __
- 30-nm structure
- fluid mosaic
- linker length
- local perturbations
- DNA-binding proteins
- nucleosomes
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· Certain types of chromatin structure can be __—passed down from a cell to its descendants
o Because the __ that reults is based on an __ rather than on a __, this is a form of __
· Chromatin structure plays a central role in the __, __, and __, including ourselves
- inherited
- cell memory
- inherited protein structure
- change in DNA sequence
- epigenetic inheritance
- development, growth, and maintenance of eukaryotic organisms
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· Biochemists had determined that mammalian chromatin consist of an approximately equal mass of __ and __, meaning that, on average, every 200 nucleotide pairs of DNA in our cells is associated with more than __ (that is, a mass of protein equivalent to the total mass of the __)
- histone and non-histone proteins
- 1000 amino acids of non-histone protein
- histone octamer plus histone H1
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· There is an amazingly slow rate of evolutionary change in the sequence of the __
o A change in any one of the __ in __must be deleterious to these organisms
· A combination of genetics and cytology had revealed that a particular form of chromatin does what?
- four core histones
- 102 amino acids in H4
- silences the genes that it packages without regard to nucleotide sequence—and doe so ina manner that is directly inherited by both daughter cells when a cell divides
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· There are two types of chromatin: a __ and a __
o __is a compact form and highly concentrated in specific regions; more than __ of the genome is packaged in this way
- highly condensed heterochromatin and a less condensed euchromatin
- Heterochromatin
- 10%
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· The DNA in heterochromatin contains very few __. And those __ that become packaged into __are __ by this type of packaging
o Heterochromatin encompasses several distinct types of chromatin structure whose common feature is an __; and, it creates __
- genes
- euchromatic genes
- heterochromatin
- turned off
- especially high degree of compaction
- different types of compact chromatin with distinct feature that make it highly resistant to gene expression for the vast majority of genes
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· When a gene that is normally expressed in __is relocated into a region of __, it ceases to be expressed, and the gene is said to be __.
o These differences in gene expression are examples of __, in which the activity of a gene depends on its position relative to a nearby region of __ on a chromosome
§ The __ associated with heterochromatin exhibit a feature called __, which in retrospect provided critical clues concerning __
- euchromatin
- heterochromatin
- silenced
- position effects
- heterochromatin
- position effects
- position effect variegation
- chromatin function
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· In drosophila, __ that directly connect a region of __to a region of __tend to __the nearby __
o The ___ spreads a different distance in different early cells in the fly embryo, but once the __condition is established on a gene, it tends to be stably __
o Excessive genetic screens have been carried out in Drosophila in search for gene products that either __ or __ and __—that is, for genes that when mutated serve as either __ or __ of __.
- chromosome breakage events
- heterochromatin
- euchromatin
- inactivate
- euchromatic genes
- zone of inactivation
- heterochromatic
- inherited by all of the cell’ progeny
- enhance or suppress the spread of heterochromatin and its stable inheritance
- enhancers or suppressors of position effect variegation
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· The detailed characterization of the proteins produced by these genes has revealed that many are __ that underlie a remarkable mechanism for __, one that requires the __, explaining the slow change in histones over time
- nonhistone chromosomal proteins
- eukaryotic gene control
- precise amino acid sequences of the core histones
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· The amino acid side chains of the __ in the __ are subjected to a remarkable variety of __, including __, __, and __.
o A large number of these side-chain modifications occur on the __that protrude from the __. However, there are also specific side-chain modifications on the nucleosome’s globular core.
- four histones
- nucleosome core
- covalent modifications
- acetylation of lysines, the mono, di, and tri-methylation of lysines, and the phosphorylation of serines
- eight relatively unstructured N-terminal “histone tails”
- nucleosome
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· All of those modifications are __. Modifications of side chains in a nucleosome are created by __, which usually act on __. A different enzyme ___.
o Ex: __add acetyl groups; histone __ remove
o __ add methyl groups and __remove
- reversible
- specific enzymes
- one or a few sites
- removes each modification
- acetyl transferases (HATs)
- deacetylase complexes (HDACs)
- Methyl transferases
- demethylases
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· The initial recruitment of these enzymes depends on __ that bind to __, and these are produced at different times in the lfie of an organism
· In some cases, the __ on nucleosomes can persist long after the __ that first induced them have disappeared, thereby carrying a memory in the cell of its developmental history. Different patterns of __ are found on different groups of __.
- gene regulatory proteins
- specific DNA sequences along chromosomes
- covalent modifications
- gene regulatory proteins
- covalent modification
- nucleosomes
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o Modification of histones are carefully controlled with important consequences.
§ The acetylation of lysines on the N-terminal tails tend to __, in part because adding an acetyl group to lysine does what?
- loosen chromatin structure
- removes its positive charge, thereby reducing the affinity of the tails for adjacent nucleosomes.
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· The most profound effect of the histone modifications is their ability to __. These new proteins determine what?
o In this way, the precise structure of a domain of chromatin determines the __, and thereby the structure and function of the eukaryotic cell
- attract specific proteins to a stretch of chromatin that has been appropariteyl modified
- how and when genes will be expressed, as well as other biological functions
expression of the genes packaged in it
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