Steroid hormone-receptor complexes regulate the transcription of specific genes. Recent studies of high-affinity interactions between the receptors and discrete regions of DNA, together with gene-transfer experiments, have led to the precise mapping of hormone regulatory elements. Nothing is known, however, about the mechanisms whereby DNA-bound receptors modulate gene transcription. At the start of transcription in prokaryotes two oligomeric molecules of several regulatory proteins must bind to two specific DNA sites and interact with one another to regulate the binding of RNA polymerase to DNA. Using electron microscopy to observe progesterone receptor binding to regulatory regions of uteroglobin and mouse mammary tumour virus genes, we demonstrate a similar binding between receptor oligomers at two DNA sites. DNA loops are formed when the hormone regulatory elements are at a distance from one another. Thus, in common with certain prokaryotic systems, protein-protein interactions may be important in steroid hormone regulation of gene transcription.

DNA↗

PubMedDate not supplied

Human placental protein 14 gene: sequence and characterization of a short duplication.

Differential hybridization of cDNAs corresponding to mRNAs expressed in the human endometrium during the secretory phase or during the first trimester of pregnancy, but not during the proliferative phase, allowed us to isolate and characterize cDNAs encoding human placental protein 14 (PP14). The cDNA was used to isolate the PP14 gene from a human genomic library. The entire gene encompasses 5.05 kb divided into seven exons by six introns. The human PP14 gene shows identical organization with the ovine beta-lactoglobulin gene, as expected from protein homology. Sequencing of 3 kb of the 5'-flanking region of the gene allowed us to characterize a 400-bp duplication of the PP14 gene lying at position -2,660. This duplication was homologous to 100 bp of exon 4 and 300 bp of intron 4, including 180 bp corresponding exactly to the right arm of an Alu element lying on the complementary strand. This homology suggests that this duplication may have arisen through a retroposition event.

Amino Acid Sequence↗

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[Nuclear receptors].

Nuclear receptors form a superfamily of transcriptional regulators including both classical hormone receptors and orphan receptors. The functional anatomy of the receptors is described as well as their interaction with coactivators, cointegrators and corepressors. Nuclear receptors activate and inhibit gene transcription by regulating histone acetylases and histone deacetylases. Receptor isoforms (oestrogen receptors alpha and beta), ligands exerting differential effects on the same receptor and the mechanism of action of antihormones are discussed.

Animals↗

PubMedDate not supplied