The alpha1-fetoprotein locus is activated by a nuclear receptor of the Drosophila FTZ-F1 family.

The alpha1-fetoprotein (AFP) gene is located between the albumin and alpha-albumin genes and is activated by transcription factor FTF (fetoprotein transcription factor), presumed to transduce early developmental signals to the albumin gene cluster. We have identified FTF as an orphan nuclear receptor of the Drosophila FTZ-F1 family. FTF recognizes the DNA sequence 5'-TCAAGGTCA-3', the canonical recognition motif for FTZ-F1 receptors. cDNA sequence homologies indicate that rat FTF is the ortholog of mouse LRH-1 and Xenopus xFF1rA. Rodent FTF is encoded by a single-copy gene, related to the gene encoding steroidogenic factor 1 (SF-1). The 5.2-kb FTF transcript is translated from several in-frame initiator codons into FTF isoforms (54 to 64 kDa) which appear to bind DNA as monomers, with no need for a specific ligand, similar KdS (approximately equal 3 x 10(-10) M), and similar transcriptional effects. FTF activates the AFP promoter without the use of an amino-terminal activation domain; carboxy-terminus-truncated FTF exerts strong dominant negative effects. In the AFP promoter, FTF recruits an accessory trans-activator which imparts glucocorticoid reactivity upon the AFP gene. FTF binding sites are found in the promoters of other liver-expressed genes, some encoding liver transcription factors; FTF, liver alpha1-antitrypsin promoter factor LFB2, and HNF-3beta promoter factor UF2-H3beta are probably the same factor. FTF is also abundantly expressed in the pancreas and may exert differentiation functions in endodermal sublineages, similar to SF-1 in steroidogenic tissues. HepG2 hepatoma cells seem to express a mutated form of FTF.

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Correction for Xu et al., The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II is a critical regulator of adipogenesis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0804101105 ◽

2008 ◽

Vol 105 (23) ◽

pp. 8161-8161

Keyword(s):

Transcription Factor ◽

Nuclear Receptor ◽

Orphan Nuclear Receptor ◽

Factor Ii ◽

Upstream Promoter ◽

Chicken Ovalbumin

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The gene encoding the transcription factor SCIP has features of an expressed retroposon.

Molecular and Cellular Biology ◽

10.1128/mcb.11.9.4642 ◽

1991 ◽

Vol 11 (9) ◽

pp. 4642-4650 ◽

Cited By ~ 36

Author(s):

R Kuhn ◽

E S Monuki ◽

G Lemke

Keyword(s):

Transcription Factor ◽

Schwann Cells ◽

Cpg Island ◽

Single Copy ◽

Gene Encoding ◽

Intronless Gene ◽

Gene Comparison ◽

Acid Protein ◽

Central Nervous Systems ◽

Glial Progenitor Cells

SCIP is a POU domain transcription factor expressed by glial progenitor cells in the peripheral and central nervous systems (dividing Schwann cells and O-2A cells, respectively), where it appears to act as a repressor of myelin-specific genes. We have isolated genomic clones encoding the rat SCIP gene. Comparison of the structure of these clones with genomic Southern blots and SCIP cDNAs demonstrates that SCIP is encoded in a single-copy, intronless gene that has the general features of an expressed retroposon. This gene contributes to an extended CpG island. It is transcribed to produce a 3.1-kb mRNA that encodes a 451-amino-acid protein with a predicted molecular mass of 45 kDa. Immunopurified SCIP antibodies specifically recognize a nuclear protein of this size in cultured proliferating Schwann cells, and gel shift analyses demonstrate that this protein is the predominant octamer-binding protein in these cells.

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The orphan nuclear receptor NGFI-B regulates expression of the gene encoding steroid 21-hydroxylase

Molecular and Cellular Biology ◽

10.1128/mcb.13.2.861-868.1993 ◽

1993 ◽

Vol 13 (2) ◽

pp. 861-868

Author(s):

T E Wilson ◽

A R Mouw ◽

C A Weaver ◽

J Milbrandt ◽

K L Parker

Keyword(s):

Nuclear Receptor ◽

Transcriptional Activation ◽

Core Promoter ◽

Orphan Nuclear Receptor ◽

Recognition Sequence ◽

Mobility Shift ◽

Adrenocortical Cells ◽

Gene Encoding ◽

Adult Rat ◽

Gel Mobility Shift

As part of its trophic action to maintain the steroidogenic capacity of adrenocortical cells, corticotropin (ACTH) increases the transcription of the cytochrome P-450 steroid hydroxylase genes, including the gene encoding steroid 21-hydroxylase (21-OHase). We previously identified several promoter elements that regulate 21-OHase gene expression in mouse Y1 adrenocortical tumor cells. One of these elements, located at nucleotide -65, closely resembles the recognition sequence of the orphan nuclear receptor NGFI-B, suggesting that NGFI-B regulates this essential steroidogenic enzyme. To explore this possibility, we first used in situ hybridization to demonstrate high levels of NGFI-B transcripts in the adrenal cortex of the adult rat. In cultured mouse Y1 adrenocortical cells, treatment with ACTH, the major regulator of 21-OHase transcription, rapidly increased NGFI-B expression. Gel mobility shift and DNase I footprinting experiments showed that recombinantly expressed NGFI-B interacts specifically with the 21-OHase -65 element and identified one complex formed by Y1 extracts and the 21-OHase -65 element that contains NGFI-B. Expression of NGFI-B significantly augmented the activity of the intact 21-OHase promoter, while mutations of the -65 element that abolish NGFI-B binding markedly diminished NGFI-B-mediated transcriptional activation. Specific mutations of NGFI-B shown previously to impair either DNA binding or transcriptional activation diminished the effect of NGFI-B coexpression on 21-OHase expression. Finally, an oligonucleotide containing the NGFI-B response element conferred ACTH response to a core promoter from the prolactin gene, showing that this element is sufficient for ACTH induction. Collectively, these results identify a cellular promoter element that is regulated by NGFI-B and implicate NGFI-B in the transcriptional induction of 21-OHase by ACTH.

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