DNA Organization in Eukaryotic Chromosomes

Chapter 12: Organization in Chromosomes

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DNA Organization in Eukaryotic Chromosomes

Chapter 12: Section 12.4


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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


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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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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 superhelix


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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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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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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


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Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.

Fig. 8.17 A possible nucleosome structure


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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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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


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Fig. 8.20b Packaging of nucleosomes into the 30-nm chromatin fiber


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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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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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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 darkly


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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 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 Eukaryotic Chromosomes

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