HUMAN ESTROGEN RECEPTOR-LIKE-1 (ESRL1) GENE - GENOMIC ORGANIZATION, CHROMOSOMAL LOCALIZATION, AND PROMOTER CHARACTERIZATION

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.