gene expression open to chapter 18. dilemma all the dna in an organism’s cells is basically the...
TRANSCRIPT
Dilemma
• All the DNA in an organism’s cells is basically the same.
• We have many of the same genes as a fruit fly (abt 60%).
• What accounts for the differentiation in the cells?
Regulation of Gene Expression
• Regulation can occur at many levels in the DNA RNA PROTEIN– Transcription– Post-Transcription– Translation– Final Folding and Refolding of Proteins
Overview
• Prokaryotes have operons• Eukaryotes
– Regulatory sequences– Selective transcription– Homeobox Genes (HOX)– Epigenome
PROKARYOTE OPERON– Promotor- Where RNA polymerase attaches– Operator- switch that turns on or off. If
repressor attaches, it is “off”. Transcription is disabled.
– Gene– Examples:
• Lac Operon- If Lactose is present, repressor inactive, gene turned on.
• Trp Operon - If Tryptophan is present, repressor active, gene turned off.
Figure 18.3b-1
(b) Tryptophan present, repressor active, operon off
DNA
mRNA
Protein
Tryptophan (corepressor)
Activerepressor
Lac and Trp Operons
• No matter which type of operon, when the repressor is active, the gene is switched___.
• When lactose is present, the gene is switched _____
• When tryptophan is present, the gene is switched ______
Lac and Trp Operons
• No matter which type of operon, when the repressor is active, the gene is switched off.
• When lactose is present, the lac gene is switched on
• When tryptophan is present, the trp gene is switched off
What would happen if the repressor of an operon were mutated so that it could not bind to the operator?
a) irreversible binding of the repressor to the promotor.
b) reduced transcription of the operon’s genes
c) continuous transcription of the operon’s genes
EUKARYOTE REGULATORY SEQUENCES
• Proteins (transcription factors) can bind to enhancer sequences on gene. Depending upon cellular conditions, this may enable gene to turn on (promote) or off (repress). Eukaryotes have multiple switches.– Induction- If proteins from neighboring cells
are present, gene may turn on (ex: retina)– Hormones and other molecules may attach to
enhancer sequence to turn on genes.
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Signal
NUCLEUSChromatin
Chromatin modification:DNA unpacking involvinghistone acetylation andDNA demethylation
DNA
Gene
Gene availablefor transcription
RNA ExonPrimary transcript
Transcription
Intron
RNA processing
Cap
Tail
mRNA in nucleus
Transport to cytoplasm
CYTOPLASM
mRNA in cytoplasm
TranslationDegradationof mRNA
Polypeptide
Protein processing, suchas cleavage and chemical modification
Active proteinDegradationof protein
Transport to cellulardestination
Cellular function (suchas enzymatic activity,structural support)
EPIGENOME• Environmental effects can impact gene
expression.• Histone Acetylation- Adding acetyl group to
histone proteins makes DNA more accessible, promoting transcription
• Methylation seems to prevent genes from loosening from histones, repressing transcription.– Twins can have different diseases, and their
gene expression becomes more divergent as they age.
HOMEOBOX GENES
• HOX genes (Homeotic genes)– Master control genes
• Segmented organisms have HOX genes associated with genes for body parts. For example, since the same genes form antenna and leg, the structure that forms depends upon its HOX master control gene.
Transcriptional control
• Name an epigenetic factor that in represses transcription.
• Name an epigenetic factor that promotes transcription.
• The reason that the same gene can code for either an antenna or a leg is that this gene is controlled by ______
SELECTIVE TRANSCRIPTION
• During transcription, intervening sequences of mRNA are removed (introns).
• Exons are spliced together. – Males and females have the same set of genes,
the fact that they are spliced differently accounts for the difference in gender.
– Splicing and DNA rearrangement account for millions of different antibodies from the same genes.
Post transcriptional ModificationRNAi
• Interference RNA- RNAi• Regulates gene expression at transcription
level, by attaching to complementary mRNA
• Often inhibits or silences.
• Forms may be called microRNA, or siRNA• See Video RNAi on Teachers Domain
(a) Primary miRNA transcript
HairpinmiRNA
miRNA
Hydrogenbond
Dicer
miRNA-proteincomplex
mRNA degraded Translation blocked
(b) Generation and function of miRNAs
5 3
Figure 18.15
Figure 18.25
Colon
Normal colonepithelial cells
Lossof tumor-suppressorgene APC(or other)
1
2
3
4
5Colon wall
Small benigngrowth(polyp)
Activationof rasoncogene
Lossof tumor-suppressorgene DCC
Lossof tumor-suppressorgene p53
Additionalmutations
Malignanttumor(carcinoma)
Largerbenign growth(adenoma)
Cancer is a multistep process -Mutations of tumor suppressor- Mutation of proto-oncogene
• See HMMI Click and Learn Genetic Switches
• http://www.hhmi.org/biointeractive/gene-switch