Download Chapter 19 (Eukaryotic Genome)

Chapter 19
EUKARYOTIC GENOMES
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In eukaryotes, the DNA-protein complex, is called:
– chromatin
– Is ordered into higher structural levels than
– The DNA-protein complex in prokaryotes
Figure 19.1
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Chromatin structure is based on successive
levels of DNA packing
• Eukaryotic DNA
– Is precisely combined with a large amount of
protein
• Eukaryotic chromosomes
– Contain an enormous amount of DNA relative
to their condensed length
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Nucleosomes, or “Beads on a String”
• Proteins called histones:
– Are responsible for the first level of DNA
packing in chromatin
– Bind tightly to DNA
• The association of DNA and histones
– Seems to remain intact throughout the cell
cycle
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In electron micrographs
– Unfolded chromatin has the appearance of beads
on a string
• Each “bead” is a nucleosome, which is:
– The basic unit of DNA packing
2 nm
DNA double helix
Histones
Histone
tails
Histone H1
Linker DNA
(“string”)
Nucleosome
(“bad”)
(a) Nucleosomes (10-nm fiber)
Figure 19.2 a
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10 nm
Higher Levels of DNA Packing
• The next level of packing
– Forms the 30-nm chromatin fiber
30 nm
Nucleosome
(b) 30-nm fiber
Figure 19.2 b
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• The 30-nm fiber, in turn
– Forms looped domains, making up a 300-nm
fiber
Protein scaffold
Loops
300 nm
(c) Looped domains (300-nm fiber)
Figure 19.2 c
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Scaffold
• In a mitotic chromosome
– The looped domains themselves coil and fold
forming the characteristic metaphase
chromosome
700 nm
1,400 nm
(d) Metaphase chromosome
Figure 19.2 d
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• Gene expression can be regulated at any
stage, but the key step is transcription
• All organisms
– Must regulate which genes are expressed at
any given time
• During development, cells of a multicellular
organism undergo a process of:
– specialization in form and function
– This process is called cell differentiation
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Differential Gene Expression
• Each cell of a multicellular eukaryote
– Expresses only a fraction of its genes
• In each type of differentiated cell
– A unique subset of genes is expressed
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Regulation of Chromatin Structure
Interphase chromatin can exist in two forms:
–
heterochromatin: “highly condensed form”.
– euchromatin: “less compacted form”
• Genes within highly packed heterochromatin
– Are usually not expressed
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Histone Modification
• Chemical modification of histone tails
– Can affect the configuration of chromatin and
thus gene expression
Chromatin changes
Transcription
RNA processing
mRNA
degradation
Translation
Protein processing
and degradation
Histone
tails
DNA
double helix
Amino acids
available
for chemical
modification
Figure 19.4a
(a) Histone tails protrude outward from a nucleosome
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Histone acetylation & deacetylation
• Acetylation loosens chromatin structure, and
– Enhances transcription
• Deacetylation condenses chromatin structure, and
– Suppresses transcription.
Unacetylated histones
Figure 19.4 b
Acetylated histones
(b) Acetylation of histone tails promotes loose chromatin structure that
permits transcription
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
DNA Methylation & Epigenetic Inheritance
• DNA methylation:
– Methyl groups addition to certain DNA bases
–
Associated with reduced transcription in some
species
• Epigenetic inheritance
– The inheritance of traits transmitted by
mechanisms not directly involving the
nucleotide sequence:
– Example: Inheritance of methylation
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Regulation of Transcription Initiation
• Carried by chromatin modifying enzymes
• They provide initial control of gene expression
by:
– making a region of DNA either more or less
able to bind the transcription machinery
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Organization of a Typical Eukaryotic Gene
• multiple control elements are associated with most
eukaryotic genes:
– Segments of noncoding DNA that help regulate
transcription by binding certain proteins
Enhancer
(distal control elements)
Poly-A signal Termination
sequence
region
Proximal
control elements
Exon
Intron
Exon
Intron
Exon
DNA
Downstream
Upstream
Promoter
Chromatin changes
Transcription
Exon
Primary RNA
5
transcript
(pre-mRNA)
Intron
Exon
RNA processing:
Cap and tail added;
introns excised and
exons spliced together
Transcription
Intron RNA
RNA processing
mRNA
degradation
Cleared 3 end
of primary
transport
Coding segment
Translation
Protein processing
and degradation
Poly-A
signal
Intron Exon
mRNA
G
P
Figure 19.5
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P
P
5 Cap 5 UTR
(untranslated
region)
Start
codon
Stop
codon
Poly-A
3 UTR
(untranslated tail
region)
The Roles of Transcription Factors
• To initiate transcription
– Eukaryotic RNA polymerase requires the
assistance of proteins called:
• transcription factors
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Enhancers and Specific Transcription Factors
• Proximal control elements
– Are located close to the promoter
• Distal control elements, groups of which are
called enhancers
– May be far away from a gene or even in
an intron
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Some specific transcription factors function as
repressors
– To inhibit expression of a particular gene
• Some activators and repressors
– Act indirectly by influencing chromatin
structure
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Protein Processing and Degradation
• After translation
– Various types of protein processing, including:
• Cleavage of chemical groups
• addition of chemical groups,
are subject to control
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cancer
• Cancer results from:
– genetic changes that affect cell cycle control
• The gene regulation systems that go wrong
during cancer are:
– the very same systems that play important
roles in:
• embryonic development
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Types of Genes Associated with Cancer
• The genes that normally regulate cell growth
and division during the cell cycle Include:
– genes for:
• Growth factors,
• Growth factors receptors, and
• Intracellular signaling pathways molecules
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Oncogenes and Proto-Oncogenes
• Oncogenes
– Are cancer-causing genes
• Proto oncogenes
– Are normal cellular genes that
– code for proteins that stimulate:
• normal cell growth and division
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Tumor-Suppressor Genes
• Tumor suppressor genes
– Encode proteins that inhibit abnormal cell
division
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Interference with Normal Cell-Signaling Pathways
• Many proto oncogenes and tumor suppressor
genes, respectively, encode components of:
– growth-stimulating pathways
– growth-inhibiting pathways
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The Multistep Model of Cancer Development
• Normal cells are converted to cancer cells
– By the accumulation of:
• multiple mutations affecting:
– proto-oncogenes and
– tumor-suppressor genes
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• Certain viruses
– Promote cancer by integration of viral DNA into
a cell’s genome
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Inherited Predisposition to Cancer
• Individuals who inherit a mutant oncogene or
tumor suppressor allele
– Have an increased risk of developing certain
types of cancer
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• Eukaryotic genomes can have many noncoding
DNA sequences in addition to genes
• The bulk of most eukaryotic genomes
– Consists of noncoding DNA sequences, often
described in the past as:
• “junk DNA”
• However, much evidence is accumulating
– That noncoding DNA plays important roles in
the cell
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Relationship Between Genomic Composition
and Organismal Complexity
• Compared with prokaryotic genomes, the
genomes of eukaryotes
– Generally are larger
– Have longer genes
– Contain a much greater amount of noncoding
DNA both associated:
• with genes and
• between genes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings