Chapter 8

Control of Gene Expression

EssentialCell Biology

FOURTH EDITION

Copyright © Garland Science 2014

Alberts • Bray • Hopkin • Johnson • Lewis • Raff • Roberts • Walter

Fig. 8-1

The vast differences in size and morphology of differentcell types is due to differences in gene expression from the same genome.

β cells of pancreas: insulinα cells of pancreas: glucagonB cells: antibodiesRBC: hemoglobinskeletal muscle: muscle actin and myosinneuron: neurotransmitters/receptorsliver: gluconeogenesis enzymes, signaling proteins

Deprogramming of terminally differentiated cells shows that all cells of a multi-cellular organism contain a full genome.

even mammals!

Fig. 8-2

Gene expression can be controlled at many levels.

Fig. 8-3

*

Transcription regulators bind specific DNA sequences

through interaction with the major groove.

Fig. 8-4 amino acids H bond with nitrogenous bases

Our earliest knowledge of transcriptional regulation came from studies in bacteria.

Bacteria have genes of related function transcribed from a single promoter.

Fig. 8-6

Translational Repressor Allosterically Regulated

product of genes activates the repressor when level in medium high

Fig. 8-7

Translational Activator Also Allosterically Regulated

cAMP signaling molecule activates the activator when level high in cell

Fig. 8-7

cAMP

CAP

Lac operon has binding sites for both an activator and a repressor.

active when lactose absent

active when lactose absentactive when

glucose absent

active when glucose absent

active when lactose absent

Activator Repressor

inactive when glucose present

inactive when glucose present

inactive when lactose present

Fig. 8-9

In eukaryotes, activators and repressors can work from a distance.

Fig. 8-10

Mediator links to preinitiation complex through DNA bending

Some activators act through altering chromatin.

Fig. 8-11

making TATA box available to TBP

Animation (0:30)

Activators and Repressors Act By Committee: Combinatorial Control

Fig. 8-12

Example of Combinatorial Control: Drosophila Embryo

Fig. 8-12

Each regulatory segment specifies particular stripe

promoter-reporter gene fusionmade by recombinant DNA technology

Each regulatory segment provides binding sites for a different set of regulatory proteins.

stripe too broad when lacking these

stripe too weak when lacking theseFig. 8-14

Specific combinations of regulatory proteins induce specific cell fates from precursor cells.

Fig. 8-12

Example: Introduction of neuron-specific regulators into liver cell induces differentiation into neuron!

Fig. 8-16

Example: Introduction of Embryonic Stem (ES) cell-specific regulators into fibroblast induces differentiation into ES-like cell(induced Pluripotent Stem cell)!

Fig. 8-18

have potential for gene therapy

A single regulatory protein can evendirect developmentof entire organ

Ey regulator expressionin leg precursor resultsin eye development in Drosophila leg!

Fig. 8-19

Cells have memory mechanisms that allow them to record a decision made after ceasing expression of a regulatory protein expressed only during early embryogenesis.

1) Feedback Loop2) DNA methylation3) Histone modification

Cell-Memory Mechanisms

Type 1) Feedback Loop

Fig. 8-20

regulatory protein regulates its own

transcription

Type 2) DNA Methylation

(Cytosine of CG dinucleotide)

Fig. 8-21, 22

Type 3) Histone Modification

Fig. 8-23 Heterochromatin proteins recruit histone modificationenzyme needed for their binding

Examples of Translational Control in Bacteria

Ribosomal proteins inhibit their L. monocytogenes mRNA containsown translation when in excess thermosensing sequence

Fig. 8-24

The genome sequencing projects and studies in model organisms have revealed the presence of many functional RNAs that are non-coding (ncRNAs)

1) micro RNAs (miRNAs)2) small interfering (siRNAs)3) long non-coding RNAs (lncRNAs)

At least one third of human protein-coding genes are regulated by miRNAs.

Fig. 8-25

RISC also targets dsRNAs from foreign transpososon and viral DNA

Fig. 8-2

In lower eukaryotes, RISC also recruits heterochromatin proteins to silence foreign DNA.

Fig. 5-30

Heterochromatin is a Heritable Inactive Chromatin State

Random expression of Xist ncRNA from Xp selects it for inactivation

Xist RNA recruits histonemodifying enzyme andHP1-like protein

Xm has equal chance of being selected

Clonal pattern of X inactivation responsible for coat pattern of calico cats