DNA Organization in Eukaryotic Chromosomes
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DNA Organization in Eukaryotic Chromosomes
DNA Organization in ChromosomesUpendra Sharma
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Eukaryotic chromosomal organization Many eukaryotes are diploid (2N) The amount of DNA that eukaryotes have varies; the
amount of DNA is not necessarily related to the complexity (Amoeba proteus has a larger amount of DNA than Homo sapiens)
Eukaryotic chromosomes are integrated with proteins that help it fold (protein + DNA = chromatin)
Chromosomes become visible during cell division DNA of a human cell is 2.3 m (7.5 ft) in length if
placed end to end while the nucleus is a few micrometers; packaging/folding of DNA is necessary
DNA Organization in ChromosomesUpendra Sharma
DNA Organization in Chromosomes 3
Eukaryotic chromosomal organization 2 main groups of proteins involved in
folding/packaging eukaryotic chromosomes Histones = positively charged proteins
filled with amino acids lysine and arginine that bond
Nonhistones = less positive
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DNA Organization in Chromosomes 4
Model for Chromatin Structure Chromatin is linked together every
200 bps (nuclease digestion) Chromatin arranged like “beads on a
string” (electron microscope) 8 histones in each nucleosome 147 bps per nucleosome core particle
with 53 bps for linker DNA (H1) Left-handed superhelixUpendra Sharma
DNA Organization in Chromosomes 5
Eukaryotic chromosomal organization Histone proteins
Abundant Histone protein sequence is highly conserved
among eukaryotes—conserved function Provide the first level of packaging for the
chromosome; compact the chromosome by a factor of approximately 7
DNA is wound around histone proteins to produce nucleosomes; stretch of unwound DNA between each nucleosome
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DNA Organization in Chromosomes 6
Eukaryotic chromosomal organization Nonhistone proteins
Other proteins that are associated with the chromosomes
Many different types in a cell; highly variable in cell types, organisms, and at different times in the same cell type
Amount of nonhistone protein varies May have role in compaction or be involved in
other functions requiring interaction with the DNA
Many are acidic and negatively charged; bind to the histones; binding may be transient
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Eukaryotic chromosomal organization Histone proteins
5 main types H1—attached to the nucleosome and
involved in further compaction of the DNA (conversion of 10 nm chromatin to 30 nm chromatin)
H2A H2B H3 H4
This structure produces 10nm chromatin
Two copies in each nucleosome ‘histone octomer’; DNA wraps around this structure1.75 times
Upendra Sharma
DNA Organization in Chromosomes 8Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Fig. 8.17 A possible nucleosome structure
Upendra Sharma
DNA Organization in Chromosomes 9Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Fig. 8.18 Nucleosomes connected together by linker DNA and H1 histone to produce
the “beads-on-a-string” extended form of chromatin
10 nm chromatin is produced in the first level of packaging.
Linker DNA
H1 Histone octomer
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DNA Organization in Chromosomes 10
Eukaryotic chromosomal organization Histone proteins
DNA is further compacted when the DNA nucleosomes associate with one another to produce 30 nm chromatin
Mechanism of compaction is not understood, but H1 plays a role (if H1 is absent, then chromatin cannot be converted from 10 to 30 nm)
DNA is condensed to 1/6th its unfolded size
Upendra Sharma
DNA Organization in Chromosomes 11Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
Fig. 8.20b Packaging of nucleosomes into the 30-nm chromatin fiber
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Eukaryotic chromosomal organization Compaction continues by forming looped
domains from the 30 nm chromatin, which seems to compact the DNA to 300 nm chromatin
Human chromosomes contain about 2000 looped domains
30 nm chromatin is looped and attached to a nonhistone protein scaffolding
DNA in looped domains are attached to the nuclear matrix via DNA sequences called MARs (matrix attachment regions)
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DNA Organization in Chromosomes 13
Fig. 8.21 Model for the organization of 30-nm chromatin fiber into looped domains
that are anchored to a nonhistone protein chromosome scaffold
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Eukaryotic chromosomal organization MARs are known to be near regions of
the DNA that are actively expressed Loops are arranged so that the DNA
condensation can be independently controlled for gene expression
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Fig. 8.22 The many different orders of chromatin packing that give rise to the highly
condensed metaphase chromosome
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DNA compaction Level of DNA compaction changes
throughout the cell cycle; most compact during M (see fig 8.22 bottom) and least compact during S
2 types of chromatin; related to the level of gene expression Euchromatin—defined originally as areas
that stained lightly Heterochromatin—defined originally as
areas that stained darklyUpendra Sharma
DNA Organization in Chromosomes 17
DNA compaction Euchromatin—chromosomes or
regions therein that exhibit normal patterns of condensation and relaxation during the cell cycle Most areas of chromosomes in active
cells Usually areas where gene expression is
occurring
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DNA Organization in Chromosomes 18
DNA compaction Heterochromatin—chromosomes or
regions therein that are condensed throughout the cell cycle
Provided first clue that parts of eukaryotic chromosomes do not always encode proteins.
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DNA Cell Cycle
At the G1/S, G2/M, and M checkpoints, cells decide whether to proceed to the next stage of the cell cycle.Regulation of cell cycle progress is mediated by cyclins and cyclin-dependent kinases (CDKs) that regulate synthesis and destruction of cyclin proteins.
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DNA Organization in Chromosomes 20Upendra Sharma
DNA Organization in Chromosomes 21Upendra Sharma
DNA Organization in Chromosomes 22Upendra Sharma