Biology Reference
In-Depth Information
negative control mechanism since it facilitates SP1 binding and promoter gene
activation by SP1.
Several other examples of promoter differences in paralogous genes are known.
Thus the human
C (
CRYGC
; 2q33-q35) crystallin
genes possess similarly located TATA boxes but the
CRYGC
gene lacks the
CCAAT box present in the
CRYGB
gene (Graw
et al
., 1993). The expression of the
human main-type histone H1 (
H1F1
; 6p21.3) genes is coordinated with DNA
replication whereas the regulation of the replacement H1 subtype H1° (
H1F0
;
22q13) gene is more complex. This difference appears to be reflected in the struc-
tures of the respective gene promoters with a CCAAT box present in the main-type
histone H1 gene promoters being absent in the H1° gene promoter (Doenecke
et
al
., 1994). Similarly, the promoters of the human mammaglobin 1 (
MGB1
) and 2
(
MGB2
) genes, which are closely linked to the related uteroglobin (
UGB
) gene on
chromosome 11q13, are homologous for the first 132 bp but then exhibit major dif-
ferences that are probably responsible for the different expression patterns of these
genes (Becker
et al
., 1998). Finally, the highly homologous human placental
(
ALPP
; 2q37) and intestinal (
ALPI
; 2q37) alkaline phosphatase genes possess sev-
eral nucleotide substitutions and deletions in their 5
B (
CRYGB
; 2q33-q35) and
flanking regions which could
account for their differing tissue specificity (Knoll
et al
., 1988).
5.1.4 Orthologous genes containing dissimilar regulatory elements
Differences between orthologous gene promoter sequences have also been
described which may explain differences in expression of the same gene in differ-
ent species. In some cases, the orthologous promoters differ with respect to the
presence or absence of specific
cis
-acting sequences or alternatively in terms of the
number of such motifs. In other cases, single base-pair substitutions have been
introduced that alter the affinity of the
cis
-acting sequences for their cognate tran-
scription factors. Orthologous genes may therefore acquire different expression
profiles in different species. Thus, the expression of the human G protein-coupled
receptor 1 (
GPR1
) gene (15q21.6) which is hippocampus-specific contrasts with
that of its rat counterpart which is not expressed in the hippocampus (Marchese
et al
., 1994). The human regulatory myosin light chain (
MYL5
; 4p16.3) gene is
expressed in human adult retina and fetal muscle but not in adult skeletal muscle
suggesting that this gene is developmentally regulated (Collins
et al
., 1992). By
contrast, the orthologue of this gene is abundantly expressed in the adult skeletal
muscle of the African green monkey, providing a good example of a gene that is
differentially expressed between humans and another primate. The tissue-spe-
cific expression of many genes is known to be determined by the presence of
enhancer elements that bind tissue-specific transcription factors. The evolution
of novel tissue specificities can therefore be investigated by comparison of the
sequences of gene regulatory elements between different species.
The human apolipoprotein A1 (
APOA1
; 11q23) gene is expressed predomi-
nantly in the liver whilst its rabbit counterpart is expressed predominantly in the
intestine. The rabbit
Apoa1
gene promoter contains two
cis
-acting elements, E2
(GGAGAAGAGAGGTCA) and E3 (GAAAGTCTCTCTTCTGTT) both similar
to enhancer sequences found in murine immunoglobulin genes, that are absent
