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Chapter 10: transcriptional regulation
Fig. 10-1
Regulation of Gene Transcription
DNA-binding proteins
• RNA polymerase binding to the transcription
initiation site (e.g., promoter)
• Regulatory protein(s) binding to other sites
(e.g., operator)
• Regulatory protein binding can positively or
negatively regulate transcription
Positive/negative regulation:
binding of activator or repressor proteins
Fig. 10-2
Regulation of Gene Transcription
DNA-binding proteins
• RNA polymerase binding to the transcription
initiation site (e.g., promoter)
• Regulatory protein(s) binding to other sites
(e.g., operator)
• Regulatory protein binding can positively or
negatively regulate transcription
• Protein affinity for DNA or for other proteins can
be influenced by allosteric conformation
Effector binding mediates allosteric change
Effector promotes
activator binding
Effector prevents
repressor binding
Fig. 10-3
Fig. 10-5
In mammalian newborns, lactose
is the principal sugar source for
intestinal flora
Lactose utilization by E. coli
• -linked disaccharide peculiar to milk
• lac genes encode a glycosidase and proteins
that promote cellular import of lactose
• Genes are transcribed only in the presence of
lactose (inducible) and the absence of glucose
(catabolite repression)
• Genes are organized into a co-transcribed cluster
(operon; encodes a polycistronic mRNA)
lac operon in E. coli
(simplified schematic)
Fig. 10-4
lac operon in E. coli
(dynamic schematic)
Fig. 10-6
Fig. 10-8
Fig. 10-9
Fig. 10-10
Effects of mutations within
consensus sequences of E. coli promoters
Fig. 10-11
Effects of lac operator mutations
Fig. 10-12
E. coli lac is also regulated by catabolite repression
• Regulates preferential utilization of glucose
• Mediated by cAMP (glucose-responsive)
• cAMP is effector of catabolite activator protein (CAP)
• cAMP-CAP binds to lac promoter, enhancing
binding of RNA polymerase
Fig. 10-13
Fig. 10-13
Activated CAP binding
induces a distortion
of its DNA binding site
“presents” P region
to RNA polymerase
Fig. 10-15
Molecular organization of the lac promoter region
Fig. 10-16
Cumulative regulatory
control of lac transcription
Fig. 10-17
Cumulative regulatory
control of lac transcription
Fig. 10-17
“Negative control”
(repression)
“Positive control”
(activation)
Fig. 10-18
Typical 5’ end sequences found in eukaryote genes
(promoter and nearby elements)
RNA polymerase
binding site
Fig. 10-22
β-globin promoter region and effects of mutation
Fig. 10-23
Consensus sequences predict important regions
which experiments can often confirm
Eukaryote polymerase binding and transcription initiation
are determined by cooperative interactions of
diverse proteins with diverse DNA sequences
Enhancer-binding factors
can be tissue-specific
Near DNA sequences: promoter-proximal elements
Fig. 10-24
Distance-independent DNA sequences: enhancers/silencers
Drosophila dpp gene region contains many tissue-specific enhancers
Visceral mesoderm enhancer (VM)
Lateral mesoderm enhancer (LE)
Fig. 10-27
Imaginal disk enhancer (ID)
Most tissue/cell-specific gene expression in eukaryotes
is controlled by enhancers
Chromosome rearrangements that
create new physical relationships
among genes can result in
gain-of-function mutation
The In(3R)Tab mutation
brings into close proximity:
• sr enhancer sequences
(drive thorax expression)
• Abd-B gene
(product drives expression
of abdominal pigmentation)
+/+
Fig. 10-28
Tab/+
Chromatin structure influences gene expression
Euchromatin: rich in active genes
Heterochromatin:
Constitutive heterochromatin (e.g., centromere regions)
few active genes
Facultative heterochromatin: euchromatin in some cells,
heterochromatic in others
rich in genes; genes are transcriptionally silent
Epigenetic inheritance: inheritance of genes with same DNA
sequence, but different levels of expression
Mammalian X-chromosome heterochromatization
• dosage compensation
• inactivation of one X in female cells
(heterochromatic X is “Barr body”)
• selection of X occurs in early embryo
(then is fixed for clonal populations)
• mammalian females mosaically express
their X-linked genes
Fig. 10-30
Imprinting: recently
discovered in mammals
DNA methylation usually
results in reduced levels
of gene expression
Differential methylation
of genes and transmission
of that methylation can
result in imprinting
phenomena
Fig. 10-32
Prader-Willi syndrome can arise “de novo”
through a combination of mutation and imprinting
Fig. 10-31
Position-effect variegation (PEV): relocation of euchromatic genes
to the vicinity of heterochromatin can result in mosaic inactivation
Fig. 10-34
Clonal-determined heterochromatin spreading
Fig. 10-
Fig. 10-