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Chapter 19 Chapter 19 Eukaryotic genomes organization, regulation and evolution http //www studiodaily com/main/searchlist/6850 html “The Inner life of the Cell” Gene expression Is altered in response[.]

Chapter 19 Eukaryotic genomes: organization,

regulation and evolution

http://www.studiodaily.com/main/searchlist/6 850.html

“The Inner life of the Cell”

Gene expression…

• Is altered in response to environmental changes, both internal and external

• Is influenced by the structure of chromatin

– Heterochromatin is highly compacted and is not

transcribed

– Euchromatin is less compacted and available for

transcription

• Is most often regulated at the transcription stage

• Differential gene expression (cell differentiation)

is the result of genes being turned “on” or “off” in different cells having the same genome

Chromatin structure….

• Eukaryotic DNA associates with many histone proteins that form complex structures – the mass of histones = the mass of DNA

• Histones – highly conserved, small, basic proteins that shape the 1st level of chromatin structure:

– The high [ ]’s of arganine and lysine make them +ly charged

– Of the 5 types (H1,H2A,H2B,H3,H4) all but H1 are found in the nucleosome, the basic unit of DNA packing

– Are evolutionarily conserved

– Only leave DNA briefly during replication

• Interphase chromatin is attached to the nuclear lamina to keep chromosomes from tangling

Eukaryotic DNA structure

• DNA + histones form

CONTROL POINTS in eukaryotic

gene expression:

• Regulation of chromatin structure: histone acetylation

and DNA methylation

• Transcription of the gene: transcription initiation

• RNA Processing: alternative RNA splicing

• mRNA export:

• mRNA degradation: polyA tail, miRNA, RNAi

• Translation of mRNA: regulatory proteins block initiation

of translation

• Polypeptide processing: cleavage, modification and

transport

• Stages in which eukaryotic gene expression can be regulated are represented by the colored boxes

Regulation of chromatin structure:

• Histone modification –

acetyl groups added to

histone tails relax

chromatin and promote

transcription

• DNA methylation can

inactivate genes and be

inherited by offspring–

genomic imprinting works

this way!

Control of gene expression in

eukaryotes: an overview

• http://highered.mcgraw-hill.com/olc/dl/120

080/bio31.swf

The eukaryotic gene consists of

• the gene + RNA polymerase + a promoter

• Control elements – non-coding DNA that regulates

transcription by binding to certain proteins Distal

elements called enhancers are very important

• Transcription factors:

– General transcription factors result in low RNA production

– Specific transcription factors can promote high levels of

transcription They may be:

• Activators – protein that stimulates transcription

• Repressors – proteins that inhibit gene expression

– Activators and repressors may alter chromatin structure, thereby further influencing gene expression

Transcription of the gene:

regulation of initiation

Prokaryotes have operons to control expression of

genes with related functions…what about

eukaryotes?

• Functionally related eukaryotic genes are co-expressed because they have the

same control elements that are activated

by the same chemical signals

Regulation of transcription

• http://wps.aw.com/bc_campbell_biology_7

/0,9854,1704975-,00.html

The mRNA transcript:

mRNA degradation:

• Eukaryotic mRNA can have a survival time measured in weeks…how is it degraded?

– Shortening of the poly-A tail and removal of

the 5’cap allows nucleases to degrade mRNA– microRNA’s can degrade mRNA or block its translation (called RNA interference)

mRNA degradation:

mRNA translation

• Initiation of translation can be blocked by regulatory proteins that bind to the UTR’s and block the attachment of ribosomes to the mRNA

Polypeptide processing:

• Any interference in the processing of the polypeptide can alter gene expression Polypeptides are processed via

– Cleavage

– Chemical modifications

– Protein transport to its target destination

Degradation of protein:

• The lifespan of a protein varies and is

strictly regulated by other proteins

• Proteins tagged with ubiquitin are

recognized by proteosomes and degraded

Protein degradation:

A review of gene expression: prokaryotes vs eukaryotes

• http://highered.mcgraw-hill.com/olc/dl/120

077/bio25.swf

Gene expression:

prokaryotic eukaryotic

RNA’s, very little “junk”

simple arrangement

controlling gene expression

response to environment; in both,

transcription initiation is the most

important control point

• Larger genome, cell specialization

• Most of the DNA does not code for protein or RNA’s

• Genome = DNA w/many proteins

Cancer results from genetic changes that

affect cell cycle control

• It is a disease in which cells escape

control methods that normally regulate cell growth and division

• The agents of change can be random

spontaneous mutations or carcinogens

• Cancer-causing genes, oncogenes, were originally discovered in retroviruses

• Proto-oncogenes code for proteins that

stimulate normal cell growth and division They may turn into oncogenes by:

– Translocation/transposition within the genome– Gene amplification

– Point mutations within a control element or the gene that may lead to a protein that is more

active or longer lived

Proto-oncogenes

Tumor-suppressor genes

• Tumor-suppressor genes encode for proteins

that help prevent uncontrolled cell division They may function to:

– Repair damaged DNA

– Control cell adhesion

– Act as components of cell-signaling pathways that

inhibit the cell cycle

• A mutation in a tumor suppressor gene reduces the activity of its protein product, leads to

Some proteins encoded by proto-oncogenes and tumor-suppressor genes are components of cell

• The product of the

p53 gene (p53

protein) inhibits the

cell cycle and allows

time for DNA repair

mechanisms to

operate Deficiencies

in this cell cycle

inhibiting pathway

Control of the cell cycle: p53 and rb

• http://highered.mcgraw-hill.com/sites/0072

437316/student_view0/chapter20/animatio ns.html#

The multistep model for cancer

development:

• Cancer results from an accumulation of

mutations, not just one

• Usually there is the presence of one active

oncogene and the mutation of several

tumor-suppressor genes

• Certain viruses can promote cancer by insertion

of viral DNA into a cells genome

• Individuals who inherit a mutant oncogene or

tumor-suppressor allele have an increased risk

of developing cancer

Eukaryotic genomes have many noncoding

DNA sequences in addition to genes

• Eukaryotes have fewer genes/DNA length than do prokaryotese

• Most of the DNA is noncoding (98.5%)

• Most intergenic DNA is repetitive DNA in the form of transposable elements and

related sequences (44%)

• There are 2 types of transposable

elements:

• This is the most prevalent type

Simple sequence DNA

• Short, noncoding DNA sequences

• Tandemly repeated

• Prominent in centromeres and telomeres

• Play a structural role in the chromosome

Multigene families:

• Collections of identical or very similar genes,

• A multigene family is a member of a family of related proteins encoded by a set of similar

genes Multigene families are believed to have arisen by duplication and variation of a single ancestral gene Examples of multigene families include those that encode the actins,

hemoglobins, immunoglobulins, and histones

The evolution of the Genome - a

• The use of transposable elements that promote

recombination, disrupt genes, or carry genes to new

locations also contributes to genome evolution