Gene Expression

Open to Chapter 18

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?

• Which genes are expressed.

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

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.

PAGE 356

Signal

NUCLEUSChromatin

Chromatin modification:DNA unpacking involvinghistone acetylation andDNA demethylation

DNA

Gene

Gene availablefor transcription

RNA ExonPrimary transcript

Transcription

IntronRNA processing

CapTail

mRNA in nucleus

Transport to cytoplasm

CYTOPLASMmRNA 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 accessibile, 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.

Normal Head Mutant Head

Transcriptional control

• Name and 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

• See Controlling Protein Synthesis AP Boardworks, Slide 4-7

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