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the activation potential of ESE-1. In the SPRR3 promoter, three transcription
factor binding sites (AP-1, ATF, and Ets) function cooperatively but these sites are
not interdependent as in the SPRR2A promoter. Thus, the loss of the proximal
Ets binding site in the SPRR3 gene promoter during the evolution of the gene
family may have been responsible for changing the promoter from one which
required highly synergistic interactions between its cognate transcription factors
to one which functions with less stringent, cooperative interactions.
Although the diversity of glycoproteins encoded by the HLA-B locus is greater
than that encoded by the HLA-A locus, the HLA-B locus promoter sequences are
more homogeneous than those of the HLA-A locus (Vallejo and Pease, 1995). We
may speculate that selection for diversity of B glycoproteins may be directly
related to the conservation of the promoter sequences and vice versa for the A gly-
coproteins and their gene promoters. Although the human HLA-A (6p21.3) and
HLA-B genes are coordinately expressed, they differ in their responsiveness to
interferon. A functional interferon-responsive element (IRE) is present in the
promoters of the HLA-B genes in the great apes but this IRE has been inactivated
by an A
T transversion in the promoters of the HLA-A genes (Vallejo et al .,
1995). Since this lesion is present in the HLA-A genes of orangutan, gorilla, chim-
panzee and human, it is likely to have occurred before the divergence of the great
apes.
The chorionic gonadotropin
gene ( CGB ; 19q13.32) has evolved by dupli-
cation of an ancestral luteinizing hormone
gene and is expressed exclusively
in the placenta. It exhibits some 94% homology with the pituitary expressed
luteinizing hormone-
( LHB ; 19q13.32) gene between coding regions and 90%
homology between promoters (Hollenberg et al ., 1994). Both LHB and CGB
genes possess TATAAA boxes at identical locations. This motif directs the ini-
tiation of an LHB transcript with a 9 nucleotide 5
UTR. The CGB gene does
not however use this box for transcriptional initiation but instead employs a
TATA-less promoter (with putative initiator element) that serves to initiate
transcription 357 bp upstream of the LHB transcriptional initiation site
(Jameson et al ., 1986). This difference in transcription site usage is evolution-
arily conserved, being found in rat, cow and human (Jameson et al ., 1986). The
experimental exchange of motifs between the two promoters has allowed the
identification of three distinct regions between
362 and +104 necessary for
placental expression of the CGB gene (Hollenberg et al ., 1994). It would appear
as if the placental expression pattern of this gene has resulted from the use of
an alternative transcriptional initiation site in conjunction with the acquisi-
tion of multiple regulatory elements that exert their effects in combinatorial
fashion.
The paralogous members of the human growth hormone gene family on chro-
mosome 17q23 differ in terms of their promoter sequences: a T
C transition at
position -112 of the CSH1 gene promoter serves to reduce binding of the pitu-
itary-specific transcription factor Pit-1 (Tansey and Catanzaro, 1991). By contrast,
the paralogous GH1, GH2 and CSH2 genes possess a T at this location within the
Pit-1 binding site. Pit-1 binding is thought to represent a negative control mech-
anism by virtue of its interference with the binding of SP1 to an adjacent site in
the promoter. The T
C transition in the CSH1 gene may thus abrogate this
 
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