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Gene Expression
Cell Differentiation
Cell types are different
because genes are
expressed differently in
them.
Causes:
 Changes in chromatin
structure
 Initiation of transcription
 RNA processing
 mRNA degradation
 Translation
 Protein processing and
degradation
Operons
 Unit of genetic function
consisting of related
clusters of genes with
related functions
 A “switch” that controls
enzyme production
 Coded for by one
transcription unit
Repressible Operons
(The trp Operon)
 Repressible Operon: always operates
unless a repressor turns it off.
 promoter: RNA polymerase binding site;
begins transcription
 operator: controls access of RNA
polymerase to genes
 transcription stops here when repressor is in place
 repressor: protein that binds to operator
and prevents attachment of RNA
polymerase
 Sometimes, a corepressor must be in place for the
repressor to be active
 Tryptophan (a.a.) synthesis
 Transcription is repressed when tryptophan
binds to the repressor, which connects to
the operator
Inducible Operons
(The lac operon)
 Inducible Operon: Always off
unless an inducer is present
 Inducer attaches to the repressor
and causes it to move so that
transcription can occur
 Lactose metabolism (lac
operon)
 lactose not present: repressor
active, operon off; no
transcription for lactose enzymes
 lactose present: repressor
inactive, operon on
 inducer molecule inactivates
protein repressor (allolactose)
Chromatin
 Complex of DNA and proteins
 DNA Packing
 histone protein (+ charged amino
acids ~ phosphates of DNA are charged)
 Nucleosome
 ”beads on a string”
 basic unit of DNA packing
 Heterochromatin
 highly condensed interphase DNA
(can not be transcribed)
 Euchromatin
 “true chromatin”
 less compacted interphase DNA
(can be transcribed)
Histone Modification
 Genes within highly packed
heterochromatin are usually not
expressed
 Chemical modifications to
histones and DNA of chromatin
influence both chromatin
structure and gene expression
 Acetylation prevents histones
from packing tightly, which allows
genes to be expressed.
 Methylation causes histones to
pack tightly so that genes are not
expressed.
Epigenetic Inheritance
 Expression of traits is not necessarily
related to the nucleotide sequence
 Some individuals may express traits
from their genes where others will not
based on histone modifications
 One twin may express a trait or get a
disease that the other does not, despite
same genes
 Schizophrenia
 Some cancers
 Etc.
Regulation of Transcription
 Control Elementsnoncoding DNA that
regulate binding proteins
 Enhancers- segments
that influence how a
gene is expressed
 Often placed far from the
actual gene
RNA and Protein
Processing
 Alternative RNA
splicing
 Different mRNA molecules
formed from the same primary
transcript
 mRNA degradation
 Protein processing
 Protein degradation
 proteasomes
Cell Differentiation
 How cells become specialized in
structure and function.
 Determinants exist in the egg cell
 Influence the expression of
characteristics in different regions of
cells
 Once cells divide by mitosis, specific
regions of the embryo will express
genes differently
Unfertilized egg cell
Sperm
Fertilization
Nucleus
Two different
cytoplasmic
determinants
Zygote
Mitotic
cell division
Two-celled
embryo
(a) Cytoplasmic determinants in the egg
Early embryo
(32 cells)
Signal
transduction
pathway
Signal
receptor
Signal
molecule
(inducer)
(b) Induction by nearby cells
NUCLEUS
Body Plan Setup
Pattern Formation
 cytoplasmic
determinants
 inductive signals
 determine spatial
organization of
tissues
Biology of Cancer
 Oncogene- cancer-causing genes
 Proto-oncogene- normal cellular genes
 How does a proto-oncogene become an oncogene?
 movement of DNA; chromosome fragments that have rejoined incorrectly
 amplification; increases the number of copies of proto-oncogenes
 point mutation; protein product more active or more resistant to degradation
 Tumor-suppressor genes
 changes in genes that prevent uncontrolled cell growth (cancer growth stimulated
by the absence of suppression)
ras and p53
 ras
 Produces Ras proteins
 Hyperactive Ras protein
causes cell cycle to
continue (increased cell
division)
 Mutations involved in
30% of all cancers
 p53
 Tumor-suppressor gene
 Activated by DNA
damage
 Turns on DNA repair or
activates “suicide” genes
 Mutations involved in
50% of all cancers