Complex 5' genomic structure of the human prolactin receptor: multiple alternative exons 1 and promoter utilization.
Transcription of the prolactin receptor (PRLR) is under the control of multiple promoters. Following the recent demonstration of the human non-coding exon 1, hE1(N) (hE1(N1)) and the generic exon 1 hE1(3), we have identified their promoters and characterized four other novel human exons 1 (hE1(N2-5)) that are alternatively spliced to a common non-coding exon 2 in human tissues and breast cancer cells. Genomic regions containing these exons, and 5'-flanking and intronic sequences, were determined and their order was established in chromosome 5p14-13. Promoters utilized in the transcription of previously characterized PRLR exons 1 species hE1(3) (hPII) and hE1(N1) (hP(N1)) were found to employ distinct mechanisms for controlling hPRLR transcription. hPIII requires C/EBP beta and Sp1/Sp3 for basal transcriptional activity, while hP(N1) activity is conferred by domains containing an Ets element and an NR half-site. The complex promoter control system that governs transcription of the hPRLR in multiple tissues is of relevance for studies on the regulation of PRLR expression in physiological and pathological states.
Hu
Zhang-Zhi
ZZ
Section on Molecular Endocrinology, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Zhuang
Li
L
Meng
Jianping
J
Tsai-Morris
Chon-Hwa
CH
Dufau
Maria L
ML
D020121:5' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004586:Electrophoresis; D005091:Exons / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D021141:Nucleic Acid Amplification Techniques; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011981:Receptors, Prolactin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009626:Terminology as Topic; D014158:Transcription, Genetic / Q000235:genetics
D020121:5' Untranslated Regions; D012333:RNA, Messenger; D011981:Receptors, Prolactin