1. Levels at which eukaryotic gene expression is controlled
Initiating or inhibiting Transcription [majority]
Transcriptional activators, coactivators, repressors
Promoters
DNA response elements, enhancers, silencers
DNA packaging and chromatin structure
Histone acetylation, histone variation
DNA methylation
Initiating or inhibiting Translation
mRNA processing, alternative splicing
RNA stability
RNA silencing
Initiating or inhibiting protein activity (Post-translational modification)

2. Found in the mature mRNA from all cell types
Constitutive exons
Not found in all mature mRNAs
Alternative exons
Intron
α-tropomyosin pre-mRNA
Exon 5′ 1 2 3 4 5 6 7 8 9 1 1 1 1 2 1 3 1 4 3′
Alternative
splicing 5′ 1 2 4 5 6 8 9 1 1 4 3′
Smooth muscle cells or 5′ 1 3 4 5 6 8 9 1 1 1 1 2 3′
Striated muscle cells
Alternatively spliced versions vary in function to meet the needs of the different cell types
Brooker, Figure 17.17

3. Splicing repressors Brooker Figure 15.17a Alternative splicing Splice
junctions S p l i c e 5′ 3′ 5′ 3′ 5′ 3′ 5′ 3′ 5′ 3′ 5′ 3′ j u n c t i o n s 5′ 1 2 3 4 3′ 5′ 1 2 3 4 3′
The spliceosome
recognizes all the
splice junctions.
A splicing repressor prevents the
recognition of a 3′-splice junction.
The next 3′-splice junction that
precedes exon 3 will be chosen.
Splicing
repressor 5′ 1 2 3 4 3′ 5′ 1 3 4 3′
All 4 exons are contained
within the mRNA.
Exon 2 is skipped and not
included in the mRNA.
Brooker Figure 15.17a
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

4. Splicing enhancers Figure 17.18b These 2 splice junctions
are not readily recognized
by the spliceosome.
Alternative
splicing
Splice
junctions
Splice
junctions 5′ 3′ 5′ 3′ 5′ 3′ 5′ 3′ 5′ 3′ 5′ 3′ 5′ 1 2 3 4 3′ 5′ 1 2 3 4 3′
The spliceosome only
recognizes 4 of the
6 splice junctions.
Splicing
enhancer
The binding of splicing enhancers
promotes the recognition of
poorly recognized junctions. All 6
junctions are recognized. 5′ 1 2 4 3′ 5′ 1 2 3 4 3′
Exon 3 is not included in the mRNA.
Exon 3 is included in the mRNA.
Figure 17.18b
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

5. Homeotic Transcription Factors: “Master Genes” turn on cascade of other genes (which developmental pathway?) WT
Homeotic Mutant

6. Homeobox (180 bp)
DNA
(a) Homeotic gene
Homeotic Genes often identify transcription factor proteins with DNA-binding Homeodomains
Transcriptional
activation domain
DNA-binding domain
(shown in orange),
the Homeodomain
(b) Homeotic protein bound to DNA
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Brooker, Fig

7. Drosophila development occurs in specific segments
Fig from iGenetics, Russell
Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings.

8. Co-linearity of Homeotic genes
Antennapedia
complex
bithorax
complex
Fly
chromosome
Co-linearity of Homeotic genes
the order of gene expression, from anterior to posterior, parallels the order of genes on the chromosome
lab pb
Dfd
Scr
Antp
Ubx
abd-A
Abd-B
Embryo
(10 hours)
Adult
Brooker, Fig 24.12

9. Did Drosophila evolution include a homeotic mutation in T3?
Dragonflies and butterflies are evolutionarily older than Drosophila
WT dragonflies and butterflies have four sets of wings

10. Drosophila have one set of Homeobox genes (“HOM-C genes”)
Specific development of each region and segment of body determined by a homeotic gene
Chromosome 6,
Mouse homeobox genes
Chromosome 11,
Chromosome 15,
Chromosome 2,
Drosophila have one set of Homeobox genes (“HOM-C genes”)
Mammals have four sets of Homeobox genes (Mammalian homeobox genes = “Hox genes”)

11. Anterior
Posterior
Occipital Cervical
Thoracic
Lumbar
Sacral
Caudal
Vertebrae
Expression pattern
Hox A1
Hox B1
Hox A3
Hox D4
Hox A4
Hox B4
Hox A5
Hox B5
Hox A6
Hox A7
Hox D8
Hox B7
Hox C9
Hox D8
Hox D9
Hox D10
Expression of Mouse Homeobox Genes (Hox) coincides with region of tissue specification
Hox D11
Hox D12
Hox D13

12. Required to Globally Pattern the
Hox10 and Hox11 Genes Are
Required to Globally Pattern the
Mammalian Skeleton
Deneen M. Wellik and Mario R. Capecchi*
Science, Vol 301, p July 2003
(An example of “reverse genetics”, where a known gene sequence is knocked out in order to determine the phenotype.)

13. Axial Skeleton Pattern in Mouse (WT)

14. Triple mutant in three Hox 10 genes: Loss of Hox-A10, Hox-C10 and Hox-D10 shows extra ribs (thoracic vertebrae) and no lumbar or sacral

15. Triple mutant in three Hox 11 genes: Loss of Hox-A11, Hox-C11 and Hox-D11 shows extra lumbar vertebrae, no sacral

16. Anterior boundary of HoxC-6 gene expression
Neck vertebrae
Mouse
Vertebrae: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
36 total vertebrae
HoxC-6
Chicken
Vertebrae: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
36 total vertebrae
HoxC-6
Goose
Vertebrae: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
44 total vertebrae
HoxC-6
Snake
Vertebrae:
No "neck," no forelimb 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Hundreds of vertebrae
HoxC-6
Brooker, Fig