title: Chromatin remodeling as a mechanism for circadian prolactin transcription: rhythmic NONO and SFPQ recruitment to HLTF.
abstract: Most clock-controlled genes (CCGs) lack the specific E-box response element necessary for direct circadian regulation. This is the case for the prolactin (Prl) gene, the expression of which oscillates in individual lactotrope pituitary cells. To characterize the processes underlying this oscillation, we used a lactotrope cell line (GH4C1 cells). In these cells, Prl gene expression fluctuated significantly during 24 h (P=0.0418). Circadian Prl transcription depended on an interaction between the pituitary-specific transcription factor, PIT-1, and the helicase-like transcription factor (HLTF), a SWI/SNF chromatin remodeler, shown here to bind the Prl promoter on an E-box that differs from the specific E-box preferentially bound by clock proteins. Circadian Prl transcription was further accompanied by marked daily chromatin transitions. While neither HLTF nor PIT-1 was rhythmically expressed, NONO and SFPQ, identified as HLTF-associated proteins by mass spectrometry, displayed a circadian pattern and bound rhythmically to the Prl promoter. Furthermore, NONO and SFPQ were functionally involved in circadian Prl transcription since overexpression of both proteins greatly reduced Prl promoter activity (P<0.001) and disrupted its circadian pattern. A mechanism involving a rhythm in paraspeckle protein recruitment is proposed to explain how the core oscillator can generate a circadian pattern of CCGs lacking the specific E-box response element.
authors.affiliation: Institut des Sciences Moleculaires de Marseille (ISM2) UMR6263 Université Aix-Marseille III, Marseille, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Guillaumond
authors.forename: Benedicte
authors.initials: B
authors.lastname: Boyer
authors.forename: Denis
authors.initials: D
authors.lastname: Becquet
authors.forename: Severine
authors.initials: S
authors.lastname: Guillen
authors.forename: Lauriane
authors.initials: L
authors.lastname: Kuhn
authors.forename: Jerome
authors.initials: J
authors.lastname: Garin
authors.forename: Maya
authors.initials: M
authors.lastname: Belghazi
authors.forename: Olivier
authors.initials: O
authors.lastname: Bosler
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Franc
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: François-Bellan
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000235:genetics* / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000378:metabolism; D024721:E-Box Elements; D006657:Histones / Q000378:metabolism; D008954:Models, Biological; D000072670:PTB-Associated Splicing Factor; D011388:Prolactin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D050817:Transcription Factor Pit-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins; D006657:Histones; D000072670:PTB-Associated Splicing Factor; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D011388:Prolactin