title: Promyelocytic leukaemia zinc finger protein (PLZF) is a glucocorticoid- and progesterone-induced transcription factor in human endometrial stromal cells and myometrial smooth muscle cells.
abstract: The promyelocytic leukaemia zinc finger (PLZF) protein belongs to the family of Krüppel-like zinc finger proteins. It is a transcriptional repressor involved in cell cycle control and has been implicated in limb development, differentiation of myeloid cells, and spermatogenesis. Little is known about the regulation of PLZF expression. In search for mediators of progesterone signalling in the female reproductive tract, we discovered induction of PLZF mRNA in primary cultures of human endometrial stromal cells and myometrial smooth muscle cells (SMC) in response to progesterone. Surprisingly, dexamethasone was a more potent inducer of PLZF expression than progesterone and elicited a sustained up-regulation of PLZF mRNA levels within 2 h. Immunofluorescence showed localization of PLZF to the nuclei of dexamethasone-treated SMC. In uterine biopsies, nuclear staining for PLZF was found in myometrial cells and endometrial stromal cells of the secretory phase. The transcriptional start site of the PLZF gene was located to position -5801 in SMC. Transfected promoter constructs containing up to 4.1 kb of 5'-flanking DNA were not induced by activated glucocorticoid or progesterone receptor. In contrast, co-transfection of c-jun and c-fos expression vectors resulted in stimulation of reporter gene activity, indicating an involvement of AP-1 transcription factors in PLZF expression.
authors.affiliation: IHF Institute for Hormone and Fertility Research, University of Hamburg, 20251 Hamburg, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Fahnenstich
authors.forename: Andreas
authors.initials: A
authors.lastname: Nandy
authors.forename: Karin
authors.initials: K
authors.lastname: Milde-Langosch
authors.forename: Tanja
authors.initials: T
authors.lastname: Schneider-Merck
authors.forename: Norbert
authors.initials: N
authors.lastname: Walther
authors.forename: Birgit
authors.initials: B
authors.lastname: Gellersen
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009215:Myometrium / Q000166:cytology*; D011374:Progesterone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D024363:Transcription Initiation Site; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C092037:ZBTB16 protein, human; D011374:Progesterone; D014212:Tretinoin; D003907:Dexamethasone