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Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse.

Publication ,  Journal Article
Teng, CT; Liu, Y; Yang, N; Walmer, D; Panella, T
Published in: Molecular endocrinology (Baltimore, Md.)
November 1992

The 5'-flanking region of the human lactoferrin gene was isolated from a human placental genomic library. This genomic clone contains a 16-kilobase pair (kbp) insert and produces seven fragments when digested with the SacI restriction enzyme. We sequenced one of the fragments that comprises 1294 bp of the 5'-flanking sequence, 79 bp of the first exon, and 690 bp of the first intron. A major transcription start site was mapped by primer extension. The region immediately upstream from the transcription initiation site following the first exon is abundant in G and C nucleotides. In the promoter and 5'-flanking region within a 300-bp stretch (-465 to -165) of the DNA, we found a noncanonical TATA box (ATAAA), CAAT-like sequence (CAAC) and sequences homologous to the consensus SP1 binding site, Pu.1/Sp.1 binding element (PU box), two half-palindromic estrogen response elements (EREs; GGTCA), an imperfect ERE (GGTCAAGGCGATC), and a sequence resembling the chicken ovalbumin upstream promoter transcription factor (COUP-TF) binding site (GTCTCACAGGTCA). The COUP-TF binding site and the imperfect ERE shared five nucleotides (GGTCA). With the exception of the two half-palindromic EREs, the elements with very well matched sequences were also found in the corresponding positions in the mouse lactoferrin gene. The synthetic oligonucleotide, including the 26 bp of COUP/ERE sequence, was cloned before the SV40 promoter in a chloramphenicol acetyltransferase reporter construct. These chimeric plasmids were transiently transfected into human endometrium carcinoma RL95-2 cells to assess hormone responsiveness. We found that the COUP/ERE element acted as an enhancer in response to estrogen stimulation. In vitro DNase I footprinting analysis showed binding of the estrogen receptor on the imperfect ERE. In contrast to the mouse lactoferrin COUP/ERE element, COUP-TF does not interact with this element, as demonstrated by band shift assay and site-directed mutagenesis. Therefore, the molecular mechanisms of the estrogen action that govern the lactoferrin gene expression differ between mouse and human.

Duke Scholars

Published In

Molecular endocrinology (Baltimore, Md.)

DOI

EISSN

1944-9917

ISSN

0888-8809

Publication Date

November 1992

Volume

6

Issue

11

Start / End Page

1969 / 1981

Related Subject Headings

  • Species Specificity
  • Sequence Homology
  • Sequence Alignment
  • Receptors, Estrogen
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Mice
  • Lactoferrin
  • Hyperplasia
  • Humans
 

Citation

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Teng, C. T., Liu, Y., Yang, N., Walmer, D., & Panella, T. (1992). Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse. Molecular Endocrinology (Baltimore, Md.), 6(11), 1969–1981. https://doi.org/10.1210/mend.6.11.1480183
Teng, C. T., Y. Liu, N. Yang, D. Walmer, and T. Panella. “Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse.Molecular Endocrinology (Baltimore, Md.) 6, no. 11 (November 1992): 1969–81. https://doi.org/10.1210/mend.6.11.1480183.
Teng CT, Liu Y, Yang N, Walmer D, Panella T. Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse. Molecular endocrinology (Baltimore, Md). 1992 Nov;6(11):1969–81.
Teng, C. T., et al. “Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse.Molecular Endocrinology (Baltimore, Md.), vol. 6, no. 11, Nov. 1992, pp. 1969–81. Epmc, doi:10.1210/mend.6.11.1480183.
Teng CT, Liu Y, Yang N, Walmer D, Panella T. Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse. Molecular endocrinology (Baltimore, Md). 1992 Nov;6(11):1969–1981.

Published In

Molecular endocrinology (Baltimore, Md.)

DOI

EISSN

1944-9917

ISSN

0888-8809

Publication Date

November 1992

Volume

6

Issue

11

Start / End Page

1969 / 1981

Related Subject Headings

  • Species Specificity
  • Sequence Homology
  • Sequence Alignment
  • Receptors, Estrogen
  • Promoter Regions, Genetic
  • Molecular Sequence Data
  • Mice
  • Lactoferrin
  • Hyperplasia
  • Humans