Hp. Shi et al., HUMAN ESTROGEN RECEPTOR-LIKE-1 (ESRL1) GENE - GENOMIC ORGANIZATION, CHROMOSOMAL LOCALIZATION, AND PROMOTER CHARACTERIZATION, Genomics, 44(1), 1997, pp. 52-60
Estrogen receptor-like 1a (ESRL1a; same as estrogen receptor-related o
rphan receptors, ERR1) belongs to a subfamily of the nuclear receptor
superfamily. We have previously shown that human ES-RL1a modulates est
rogen responsiveness of the lactoferrin gene promoter in transiently t
ransfected endometrial carcinoma RL95-2 cells. In this study, we clone
d and characterized the human ESRL1 gene. Through the fluorescence in
situ hybridization method, the ESRL1 gene was localized to the centrom
ere region of chromosome 11q12. Partial sequencing, restriction mappin
g, and PCR analysis revealed that the ESRL1 gene consists of seven exo
ns and is approximately 20 kb in length. We found that the smallest ex
on (exon 3) contains 117 bp and the largest exon (exon 7) has 1032 bp.
The smallest intron (intron 5) is only 88 bp long and the largest int
ron (intron 2) is 8 kb long. All introns have the conserved GT and AG
dinucleotides present at the donor and acceptor sites, respectively. L
ike the estrogen receptor, the highly conserved DNA-binding domain of
hESRL1a is encoded by exon 2 and exon 3, and the intron/exon junctions
(2 and 3) are well conserved between the two genes. Primer extension
analysis revealed multiple transcription initiation start sites in hum
an uterine (HeLa, HEC, and RL95-2) cell lines. However, one major init
iation start site was found by RNase protection assay. The hESRL1a mRN
A is differentially expressed in various human tissues. The nucleotide
sequence adjacent to the transcription start sites of the ESRL1 lacks
the typical TATA and CAAT boxes but is GC rich and contains 10 consen
sus Sp1-binding elements and two E boxes. The region that contains the
se transcription factor-binding elements showed a high level of promot
er activity when transiently transfected into RL95-2 cells. (C) 1997 A
cademic Press.