Gene regulation is how a cell controls which genes, out of the many genes in its genome, are "turned on" (expressed). Thanks to gene regulation, each cell type in your body has a different set of active genes – despite the fact that almost all the cells of your body contain the exact same DNA. These different patterns of gene expression cause your various cell types to have different sets of proteins, making each cell type uniquely specialized to do its job. [Source: https://www.khanacademy.org/science/biology/gene-regulation/gene-regulation-in-eukaryotes/a/overview-of-eukaryotic-gene-regulation]

1. REGULATION OF GENE
EXPRESSION

2. Gene Expression
• The process by w/c the information
encoded in a gene is converted to a
protein that determines an organism’s
characteristics & functioning.

4. The Central Dogma of Molecular
Biology
DNA RNA Protein Trait
Transferring genetic information into protein.

5. Seven Processes That Affect the Steady-
State Concentration of a Protein

6. Trends in Understanding Gene
Regulation
• Past focus has been on understanding
transcription initiation.
• There is increasing elucidation of
posttranscriptional and translational
regulation.
• Regulation relies on precise protein-DNA
and protein-protein contacts.

7. The Vocabulary of Gene Regulation
• Housekeeping gene
– under constitutive expression
– constantly expressed in approximately all cells
• Regulated gene
– Levels of the gene product rise and fall with the
needs of the organism.
– Such genes are inducible.
• able to be turned on
– Such genes are also repressible.
• able to be turned off

8. Genes and Regulatory Elements
• Structural genes: encoding proteins
• Regulatory genes: encoding products that
interact with other sequences and affect the
transcription and translation of these sequences
• Regulatory elements: DNA sequences that are
not transcribed but play a role in regulating other
nucleotide sequences

9. Control of Gene Expression
• Controlling gene expression is often
accomplished by controlling transcription
initiation.
• Regulatory proteins bind to DNA to either
block or stimulate transcription, depending
on how they interact with RNA
polymerase.

10. 10
Control of Gene Expression
• Prokaryotic organisms regulate gene
expression in response to their
environment.
• Eukaryotic cells regulate gene expression
to maintain homeostasis in the organism.

11. 11
Regulatory Proteins
• Gene expression is often controlled by
regulatory proteins binding to specific
DNA sequences.
–regulatory proteins gain access to the
bases of DNA at the major groove
–regulatory proteins possess DNA-
binding motifs

12. DNA-Binding Proteins
• Domains: 60 ~ 90 amino acids, responsible for
binding to DNA, forming hydrogen bonds with
DNA
• Distinctive types of DNA-binding proteins based
on the motif
• Motif: within the binding domain, a simple
structure that fits into the major groove of the
DNA

18. Operons
• Operator – a segment of DNA that controls the
access of RNA polymerase to the genes. Found
within the promoter sequence. (on/off switch)
• Operon- the operator, promoter, and genes they
control- the entire stretch of DNA required for
metabolic pathway. (trp operon)

19. 19
Prokaryotic Regulation
• Control of transcription initiation can be:
–positive control – increases
transcription when activators bind DNA
–negative control – reduces
transcription when repressors bind to
DNA regulatory regions called
operators

20. Prokaryotic Regulation
• Prokaryotic cells often respond to their
environment by changes in gene
expression.
• Genes involved in the same metabolic
pathway are organized in operons.
• Some operons are induced when the
metabolic pathway is needed.
• Some operons are repressed when the
metabolic pathway is no longer needed.

21. 21
Prokaryotic Regulation
• The lac operon contains genes for the
use of lactose as an energy source.
• Regulatory regions of the operon include
the CAP binding site, promoter, and the
operator.
• The coding region contains genes for 3
enzymes:
b-galactosidase, permease, and
transacetylase

22. 22

23. 23
Prokaryotic Regulation
• The lac operon is negatively regulated by
a repressor protein:
–lac repressor binds to the operator to
block transcription
–in the presence of lactose, an inducer
molecule binds to the repressor protein
–repressor can no longer bind to operator
–transcription proceeds

24. 24

25. 25

26. 26
Prokaryotic Regulation
• In the presence of both glucose and lactose,
bacterial cells prefer to use glucose.
• Glucose prevents induction of the lac operon.
–binding of CAP – cAMP complex to the
CAP binding site is required for induction
of the lac operon
–high glucose levels cause low cAMP levels
–high glucose  low cAMP  no induction
Catabolite activator protein (CAP)

27. Positive control and catabolite repression
• Catabolite repression: using glucose when
available, and repressing the metabolite of other
sugars
• This is a positive control mechanism: The
positive effect is activated by catabolite activator
protein (CAP). cAMP is binded to CAP, together
CAP–cAMP complex binds to a site slightly
upstream from the lac gene promoter.

28. Positive control and catabolite repression
• cAMP – adenosine-3′,5′-cyclic monophosphate
• The concentration of cAMP is inversely
proportional to the level of available glucose.

29. 29

30. 30

31. 31
Prokaryotic Regulation
• The trp operon encodes genes for the
biosynthesis of tryptophan.
• The operon is not expressed when the cell
contains sufficient amounts of tryptophan.
• The operon is expressed when levels of
tryptophan are low.

32. 32
Prokaryotic Regulation
• The trp operon is negatively regulated by
the trp repressor protein
–trp repressor binds to the operator to
block transcription
–binding of repressor to the operator
requires a corepressor which is
tryptophan
–low levels of tryptophan prevent the
repressor from binding to the operator

33. 33

34. 34

35. 35
Eukaryotic Regulation
• Controlling the expression of eukaryotic
genes requires transcription factors.
– general transcription factors are
required for transcription initiation
• required for proper binding of RNA
polymerase to the DNA
– specific transcription factors increase
transcription in certain cells or in
response to signals

36. 36

37. 37
Eukaryotic Transcription
• General transcription factors bind to the
promoter region of the gene.
• RNA polymerase II then binds to the
promoter to begin transcription at the start
site (+1).
• Enhancers are DNA sequences to which
specific transcription factors (activators)
bind to increase the rate of transcription.

38. 38

39. 39
Eukaryotic Transcription
• Coactivators and mediators are also
required for the function of transcription
factors.
–coactivators and mediators bind to
transcription factors and bind to other
parts of the transcription apparatus

40. 40