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Figure 19-01
LE 19-2
DNA double helix
Histone
tails
His-
tones
Linker DNA
(“string”)
Nucleosome
(“bead”)
10 nm
2 nm
Histone H1
Nucleosomes (10 nm fiber)
30 nm
Nucleosome
30-nm fiber
300 nm
Loops
Scaffold
Protein scaffold
Looped domains (300-nm fiber)
Metaphase chromosome
700 nm
1,400 nm
LE 19-2a
DNA double helix
Histone
tails
His-
tones
Linker DNA
(“string”)
Nucleosome
(“bead”)
10 nm
2 nm
Histone H1
Nucleosomes (10-nm fiber)
LE 19-2b
30 nm
Nucleosome
30-nm fiber
LE 19-2c
300 nm
Loops
Scaffold
Protein scaffold
Looped domains (300-nm fiber)
LE 19-2d
Metaphase chromosome
700 nm
1,400 nm
LE 19-3
Signal
NUCLEUS
DNA
RNA
Chromatin
Gene available
for transcription
Gene
Exon
Intro
Transcription
Primary transcript
RNA processing
Cap
Tail
mRNA in nucleus
Transport to cytoplasm
CYTOPLASM
mRNA in cytoplasm
Translation
Degradation
of mRNA
Polypeptide
Cleavage
Chemical modification
Transport to cellular
destination
Degradation of protein
Active protein
Degraded protein
Chromatin modification:
DNA unpacking involving
histone acetylation and
DNA demethylation
LE 19-4
Histone
tails
Amino acids
available
for chemical
modification
DNA
double helix
Histone tails protrude outward from a nucleosome
Acetylation of histone tails promotes loose chromatin
structure that permits transcription
Unacetylated histones Acetylated histones
LE 19-4a
Histone
tails
Amino acids
available
for chemical
modification
DNA
double helix
Histone tails protrude outward from a nucleosome
LE 19-4b
Acetylation of histone tails promotes loose chromatin
structure that permits transcription
Unacetylated histones Acetylated histones
LE 19-5
Enhancer
(distal control elements)
Proximal
control elements
Upstream
DNA
Promoter
Exon Intron Exon Intron Exon
Downstream
Transcription
Poly-A signal
sequence
Termination
region
Intron Exon Intron Exon
RNA processing:
Cap and tail added;
introns excised and
exons spliced together
Poly-A signal
Cleaved 3′ end
of primary
transcript
3′
Poly-A
tail
3′ UTR
(untranslated
region)
5′ UTR
(untranslated
region)
Start
codon
Stop
codon
Coding segment
Intron RNA
5′ Cap
mRNA
Primary RNA
transcript
(pre-mRNA)
5′
Exon
LE 19-6
Distal control
element Activators
Enhancer
DNA
DNA-bending
protein
TATA
box
Promoter
Gene
General
transcription
factors
Group of
mediator proteins
RNA
polymerase II
RNA
polymerase II
RNA synthesis
Transcription
Initiation complex
LE 19-7
Control
elements
Enhancer Promoter
Albumin
gene
Crystallin
gene
Available
activators
Available
activators
Albumin
gene not
expressed
Albumin
gene
expressed
Liver cell Lens cell
Crystallin gene
not expressed Crystallin gene
expressed
Liver cell
nucleus
Lens cell
nucleus
LE 19-8
Primary
RNA
transcript
DNA
or
Exons
RNA splicing
mRNA
LE 19-9
Dicer
Hydrogen
bond
Protein
complex
miRNA
Target mRNA
Degradation of mRNA
OR
Blockage of translation
LE 19-10
Protein to
be degraded
Ubiquitinated
protein
Proteasome
Protein entering a
proteasome
Protein
fragments
(peptides)
Proteasome
and ubiquitin
to be recycled
Ubiquitin
LE 19-11
Proto-oncogene
DNA
Translocation or transposition:
gene moved to new locus,
under new controls
New
promoter
Gene amplification:
multiple copies of the gene
Point mutation
within a control
element
Oncogene Oncogene
Point mutation
within the gene
Normal growth-stimulating
protein in excess
Normal growth-stimulating
protein in excess
Normal growth-stimulating
protein in excess
Hyperactive or
degradation-
resistant protein
LE 19-12_1
Cell cycle-stimulating
pathway
Growth
factor
G protein
Receptor
MUTATION
Protein kinases
(phosphorylation
cascade)
NUCLEUS
Hyperactive
Ras protein
(product of
oncogene
issues signals
on its own.
Transcription
factor (activator)
DNA
Gene expression
Protein that
stimulates
the cell cycle
LE 19-12_2
Active
form
of p53
DNA
DNA damage
in genome
UV
light
Protein kinases
MUTATION
Defective or
missing
transcription
factor, such as
p53, cannot
activate
transcription
Protein kinases
(phosphorylation
cascade)
Cell cycle-inhibiting
pathway
Cell cycle-stimulating
pathway
Protein that
stimulates
the cell cycle
NUCLEUS
DNA
Gene expression
Transcription
factor (activator)
Receptor
G protein
Growth
factor
MUTATION
Hyperactive
Ras protein
(product of
oncogene)
issues signals
on its own
Protein that
inhibits
the cell cycle
LE 19-12_3
Protein overexpressed
EFFECTS OF MUTATIONS
Protein absent
Cell cycle not
inhibited
Increased cell
division
Cell cycle overstimulate
Effects of
mutations
Active
form
of p53
DNA
DNA damage
in genome
UV
light
Protein kinases
MUTATION
Defective or
missing
transcription
factor, such as
p53, cannot
activate
transcription
Protein kinases
(phosphorylation
cascade)
Cell cycle-inhibiting
pathway
Cell cycle-stimulating
pathway
Protein that
inhibits
the cell cycle
NUCLEUS
DNA
Gene expression
Transcription
factor (activator)
Receptor
G protein
Growth
factor
MUTATION
Hyperactive
Ras protein
(product of
oncogene)
issues signals
on its own
Protein that
stimulates
the cell cycle
LE 19-13
Colon
Colon wall
Loss of
tumor-
suppressor
gene APC (or
other)
Normal colon
epithelial cells
Small benign
growth (polyp)
Larger benign
growth (adenoma)
Activation of
ras oncogene
Loss of
tumor-
suppressor
gene DCC
Loss of
tumor-
suppressor
gene p53
Additional
mutations
Malignant tumor
(carcinoma)
LE 19-14
Exons (regions of genes coding
for protein, rRNA, or tRNA) (1.5%)
Alu elements
(10%)
Simple sequence
DNA (3%)
Large-segment
duplications (5–6%)
Unique
noncoding
DNA (15%)
Introns and
regulatory
sequences
(24%)
Repetitive
DNA that
includes
transposable
elements
and related
sequences
(44%)
Repetitive
DNA
unrelated to
transposable
elements
(about 15%)
Figure 19-15
LE 19-16
DNA of genome
Transposon
is copied
Mobile transposon
Transposon
Insertion
New copy of
transposon
Transposon movement (“copy-and-paste” mechanism)
Retrotransposon movement
DNA of genome
Insertion
RNA
Reverse
transcriptase
Retrotransposon
New copy of
retrotransposon
LE 19-16a
DNA of genome
Transposon
is copied
Mobile transposon
Transposon
Insertion
New copy of
transposon
Transposon movement (“copy-and-paste” mechanism)
LE 19-16b
Retrotransposon movement
DNA of genome
Insertion
RNA
Reverse
transcriptase
Retrotransposon
New copy of
retrotransposon
LE 19-17
DNA
Non-transcribed
spacer
RNA transcripts
Transcription unit
DNA
18S 5.8S 28S
rRNA
18S
5.8S
28S
Part of the ribosomal RNA gene family
Heme
Hemoglobin
α-Globin
β-Globin
α-Globin gene family β-Globin gene family
Chromosome 11Chromosome 16
ζ ψζ ψα2 ψα1 α1α2
ψβ δ βGγ∍ Aγ
Embryo Embryo Fetus Adult
Fetus
and adult
The human α-golbin and β-globin gene families
LE 19-17a
DNA
Non-transcribed
spacer
RNA transcripts
Transcription unit
DNA
18S 5.8S 28S
rRNA
18S
5.8S
28S
Part of the ribosomal RNA gene family
LE 19-17b
Heme
Hemoglobin
α-Globin
β-Globin
α-Globin gene family β-Globin gene family
Chromosome 11Chromosome 16
ζ ψζ ψα2 ψα1 α1α2
ψβ δ βGγ
∍
Aγ
Embryo Embryo Fetus Adult
Fetus
and adult
The human α-globin and β-globin gene families
LE 19-18
Nonsister
chromatids
Transposable
element
Gene
Crossover
Incorrect pairing
of two homologues
during meiosis
and
LE 19-19
Duplication of
ancestral gene
Mutation in
both copies
Transposition
to different
chromosomes
Further
duplications
and mutations
Ancestral globin gene
ζ ψζ ψα2
ψα1 α1α2
ψβ δ βGγ∍ Aγ
α-Globin gene family
on chromosome 16
ψϑ
β-Globin gene family
on chromosome 11
ζ α
α
α β
β
∍
βγ
Evolutionarytime
Table 19-1
LE 19-20
Epidermal growth
factor gene with multiple
EGF exons (green)
EGF EGF EGF EGF
F F F F
Fibronectin gene with multiple
“finger” exons (orange)
K
K KEGFF
Plasminogen gene with a
“kringle” exon (blue)
Portions of ancestral genes TPA gene as it exists today
Exon
shuffling
Exon
shuffling
Exon
duplication

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Regulación de la expresión génica

  • 2.
  • 3.
  • 4.
  • 5.
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
  • 12. LE 19-2 DNA double helix Histone tails His- tones Linker DNA (“string”) Nucleosome (“bead”) 10 nm 2 nm Histone H1 Nucleosomes (10 nm fiber) 30 nm Nucleosome 30-nm fiber 300 nm Loops Scaffold Protein scaffold Looped domains (300-nm fiber) Metaphase chromosome 700 nm 1,400 nm
  • 13. LE 19-2a DNA double helix Histone tails His- tones Linker DNA (“string”) Nucleosome (“bead”) 10 nm 2 nm Histone H1 Nucleosomes (10-nm fiber)
  • 15. LE 19-2c 300 nm Loops Scaffold Protein scaffold Looped domains (300-nm fiber)
  • 17. LE 19-3 Signal NUCLEUS DNA RNA Chromatin Gene available for transcription Gene Exon Intro Transcription Primary transcript RNA processing Cap Tail mRNA in nucleus Transport to cytoplasm CYTOPLASM mRNA in cytoplasm Translation Degradation of mRNA Polypeptide Cleavage Chemical modification Transport to cellular destination Degradation of protein Active protein Degraded protein Chromatin modification: DNA unpacking involving histone acetylation and DNA demethylation
  • 18. LE 19-4 Histone tails Amino acids available for chemical modification DNA double helix Histone tails protrude outward from a nucleosome Acetylation of histone tails promotes loose chromatin structure that permits transcription Unacetylated histones Acetylated histones
  • 19. LE 19-4a Histone tails Amino acids available for chemical modification DNA double helix Histone tails protrude outward from a nucleosome
  • 20. LE 19-4b Acetylation of histone tails promotes loose chromatin structure that permits transcription Unacetylated histones Acetylated histones
  • 21.
  • 22. LE 19-5 Enhancer (distal control elements) Proximal control elements Upstream DNA Promoter Exon Intron Exon Intron Exon Downstream Transcription Poly-A signal sequence Termination region Intron Exon Intron Exon RNA processing: Cap and tail added; introns excised and exons spliced together Poly-A signal Cleaved 3′ end of primary transcript 3′ Poly-A tail 3′ UTR (untranslated region) 5′ UTR (untranslated region) Start codon Stop codon Coding segment Intron RNA 5′ Cap mRNA Primary RNA transcript (pre-mRNA) 5′ Exon
  • 23. LE 19-6 Distal control element Activators Enhancer DNA DNA-bending protein TATA box Promoter Gene General transcription factors Group of mediator proteins RNA polymerase II RNA polymerase II RNA synthesis Transcription Initiation complex
  • 24. LE 19-7 Control elements Enhancer Promoter Albumin gene Crystallin gene Available activators Available activators Albumin gene not expressed Albumin gene expressed Liver cell Lens cell Crystallin gene not expressed Crystallin gene expressed Liver cell nucleus Lens cell nucleus
  • 27. LE 19-10 Protein to be degraded Ubiquitinated protein Proteasome Protein entering a proteasome Protein fragments (peptides) Proteasome and ubiquitin to be recycled Ubiquitin
  • 28. LE 19-11 Proto-oncogene DNA Translocation or transposition: gene moved to new locus, under new controls New promoter Gene amplification: multiple copies of the gene Point mutation within a control element Oncogene Oncogene Point mutation within the gene Normal growth-stimulating protein in excess Normal growth-stimulating protein in excess Normal growth-stimulating protein in excess Hyperactive or degradation- resistant protein
  • 29. LE 19-12_1 Cell cycle-stimulating pathway Growth factor G protein Receptor MUTATION Protein kinases (phosphorylation cascade) NUCLEUS Hyperactive Ras protein (product of oncogene issues signals on its own. Transcription factor (activator) DNA Gene expression Protein that stimulates the cell cycle
  • 30. LE 19-12_2 Active form of p53 DNA DNA damage in genome UV light Protein kinases MUTATION Defective or missing transcription factor, such as p53, cannot activate transcription Protein kinases (phosphorylation cascade) Cell cycle-inhibiting pathway Cell cycle-stimulating pathway Protein that stimulates the cell cycle NUCLEUS DNA Gene expression Transcription factor (activator) Receptor G protein Growth factor MUTATION Hyperactive Ras protein (product of oncogene) issues signals on its own Protein that inhibits the cell cycle
  • 31. LE 19-12_3 Protein overexpressed EFFECTS OF MUTATIONS Protein absent Cell cycle not inhibited Increased cell division Cell cycle overstimulate Effects of mutations Active form of p53 DNA DNA damage in genome UV light Protein kinases MUTATION Defective or missing transcription factor, such as p53, cannot activate transcription Protein kinases (phosphorylation cascade) Cell cycle-inhibiting pathway Cell cycle-stimulating pathway Protein that inhibits the cell cycle NUCLEUS DNA Gene expression Transcription factor (activator) Receptor G protein Growth factor MUTATION Hyperactive Ras protein (product of oncogene) issues signals on its own Protein that stimulates the cell cycle
  • 32. LE 19-13 Colon Colon wall Loss of tumor- suppressor gene APC (or other) Normal colon epithelial cells Small benign growth (polyp) Larger benign growth (adenoma) Activation of ras oncogene Loss of tumor- suppressor gene DCC Loss of tumor- suppressor gene p53 Additional mutations Malignant tumor (carcinoma)
  • 33. LE 19-14 Exons (regions of genes coding for protein, rRNA, or tRNA) (1.5%) Alu elements (10%) Simple sequence DNA (3%) Large-segment duplications (5–6%) Unique noncoding DNA (15%) Introns and regulatory sequences (24%) Repetitive DNA that includes transposable elements and related sequences (44%) Repetitive DNA unrelated to transposable elements (about 15%)
  • 35. LE 19-16 DNA of genome Transposon is copied Mobile transposon Transposon Insertion New copy of transposon Transposon movement (“copy-and-paste” mechanism) Retrotransposon movement DNA of genome Insertion RNA Reverse transcriptase Retrotransposon New copy of retrotransposon
  • 36. LE 19-16a DNA of genome Transposon is copied Mobile transposon Transposon Insertion New copy of transposon Transposon movement (“copy-and-paste” mechanism)
  • 37. LE 19-16b Retrotransposon movement DNA of genome Insertion RNA Reverse transcriptase Retrotransposon New copy of retrotransposon
  • 38. LE 19-17 DNA Non-transcribed spacer RNA transcripts Transcription unit DNA 18S 5.8S 28S rRNA 18S 5.8S 28S Part of the ribosomal RNA gene family Heme Hemoglobin α-Globin β-Globin α-Globin gene family β-Globin gene family Chromosome 11Chromosome 16 ζ ψζ ψα2 ψα1 α1α2 ψβ δ βGγ∍ Aγ Embryo Embryo Fetus Adult Fetus and adult The human α-golbin and β-globin gene families
  • 39. LE 19-17a DNA Non-transcribed spacer RNA transcripts Transcription unit DNA 18S 5.8S 28S rRNA 18S 5.8S 28S Part of the ribosomal RNA gene family
  • 40. LE 19-17b Heme Hemoglobin α-Globin β-Globin α-Globin gene family β-Globin gene family Chromosome 11Chromosome 16 ζ ψζ ψα2 ψα1 α1α2 ψβ δ βGγ ∍ Aγ Embryo Embryo Fetus Adult Fetus and adult The human α-globin and β-globin gene families
  • 42. LE 19-19 Duplication of ancestral gene Mutation in both copies Transposition to different chromosomes Further duplications and mutations Ancestral globin gene ζ ψζ ψα2 ψα1 α1α2 ψβ δ βGγ∍ Aγ α-Globin gene family on chromosome 16 ψϑ β-Globin gene family on chromosome 11 ζ α α α β β ∍ βγ Evolutionarytime
  • 44. LE 19-20 Epidermal growth factor gene with multiple EGF exons (green) EGF EGF EGF EGF F F F F Fibronectin gene with multiple “finger” exons (orange) K K KEGFF Plasminogen gene with a “kringle” exon (blue) Portions of ancestral genes TPA gene as it exists today Exon shuffling Exon shuffling Exon duplication

Editor's Notes

  1. Estructura del operón.
  2. Estructura del operón triptófano
  3. Regulación positiva. La proteína CAP es una proteína reguladora que activa genes catabólicos). Cuando hay glucosa en E.coli los niveles de AMPc son bajos y el complejo CAP-AMPc no se forma. Cuando la glucosa se agota, aumentan los niveles de AMPc y se forma el complejo CAP-AMPc uniéndose al promotor, permitiendo la transcripción.
  4. Silenciamiento del ARN: ARNi micro ARN: ARNss de 21 a 25 nucleótidos con capacidad de regular la trasncripción por interferencia al unirse por complementariedad a ARNm bloqueando la transcripción o permitiendo la degradación del ARNm. Tienen una importante función en la defensa contra la invasión de los virus y en el silenciamiento de los transposones. ARNmi: 19 a 14 nucleótidos bloqueando la traducción
  5. regulación post-traduccional.
  6. Barbara McClintock y los transposones. Maíz con variaciones en la pigmentación por causa de elementos transponibles