Biology Reference
In-Depth Information
HSPA1A
SP1 CCAAT AP2
HSE
CCAAT
SP1
TATA AP2
i
- 158
- 105
-28
0
-74
MT2A
GRE
AP2
AP2
MRE
MRE
AP2
AP1
MRE SP1
TATA
i
- 300
- 250
- 200
- 150
- 100
- 50
0
Figure 1.3.
Transcriptional control elements upstream of the transcriptional initiation site
in the human heat shock protein 1 (
HSPA1A
; 6p21.3) and metallothionein 2A (
MT2A
;
16q13) genes. The TATA, SP1, and CCAAT boxes bind transcription factors that are
involved in constitutive transcription whilst the glucocorticoid response element (GRE),
metal response element (MRE), heat shock element (HSE), and the AP1 and AP2 sites
bind factors involved in the induction of gene expression in response to specific stimuli.
CM P
R
CNS
S
G
0
500
1000
1500
2000
2500 kb
2
5
10 15 20
R1
30
40
CNS1
45
50
55
S1
60
70
79
C1
M1
P1
G1
Dp427
Dp260
Dp140
Dp116
Dp71
Figure 1.4.
Alternative promoter usage in the human dystrophin (DMD) gene (redrawn
from Strachan and Read 1996). The alternative promoters are: C, cortical; M, muscle; P,
Purkinje; R, retinal; CNS, central nervous system; S, Schwann cell; G, Glial cell. The 79
exons of the DMD gene are denoted by bars. The first exon used to encode each isoform
is given the suffix 1, that is S1 denotes the first exon incorporated as a result of Schwann
cell promoter usage. Dystrophin isoforms are denoted by Dp acronyms.
intron of the human
ADA
gene; Aronow
et al
., 1989). Some promoters may even be
found buried within the introns of other genes (e.g. an element of the human
CYP21
gene promoter lies within intron 35 of the
C4A
gene; Tee
et al
., 1995).
The transcriptional initiation site is usually preceded by
constitutive promoter ele-
ments
of defined sequence, for example the TATA box (TATAAA; 25-30 bp 5
to the
cap site), initiator element (Py Py A
+1
N T/A Py Py) which serves as a functional
analogue of the TATA box in TATA-less promoters (Lo and Smale 1996) and the
CCAAT motif (~90 bp 5
to the cap site) which potentiate a basal level of gene
expression. Further upstream regulatory motifs bind tissue-specific transcription
factors, some binding different factors in different tissues.
Response elements
, as the
name suggests, are able to confer transcriptional responsiveness to various external
