DNA Organization in

Eukaryotic Chromosomes

Chapter 12: Section 12.4

Chapter 12: Organization in Chromosomes 1

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

Chapter 12: Organization in Chromosomes 2

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

Chapter 12: Organization in Chromosomes 3

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
Chapter 12: Organization in Chromosomes 4
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

Chapter 12: Organization in Chromosomes 5

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

Chapter 12: Organization in Chromosomes 6

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 Two copies in each nucleosome
 H4 ‘histone octomer’; DNA wraps
 This structure produces
around 10nm chromatin
this structure1.75 times

Chapter 12: Organization in Chromosomes 7

Fig. 8.17 A possible nucleosome structure

Chapter 12: Organization in Chromosomes 8

Peter 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

Histone octomer
H1

Linker DNA
10 nm chromatin is produced in the first level of packaging.
Chapter 12: Organization in Chromosomes 9
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
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

Chapter 12: Organization in Chromosomes 10

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

Chapter 12: Organization in Chromosomes 11

Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.
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)
Chapter 12: Organization in Chromosomes 12
Fig. 8.21 Model for the organization of 30-nm chromatin fiber into looped
domains
that are anchored to a nonhistone protein chromosome scaffold

Chapter 12: Organization in Chromosomes 13

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

Chapter 12: Organization in Chromosomes 14

Fig. 8.22 The many different orders of chromatin packing that give rise to the
highly
condensed metaphase chromosome

Chapter 12: Organization in Chromosomes 15

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
Chapter 12: Organization in Chromosomes 16
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

Chapter 12: Organization in Chromosomes 17

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.

Chapter 12: Organization in Chromosomes 18

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.

Chapter 12: Organization in Chromosomes 19

Chapter 12: Organization in Chromosomes 20
Chapter 12: Organization in Chromosomes 21
Chapter 12: Organization in Chromosomes 22