title: DNA methylation and transcription in a distal region upstream from the bovine AlphaS1 casein gene after once or twice daily milking.
abstract: Once daily milking (ODM) induces a reduction in milk production when compared to twice daily milking (TDM). Unilateral ODM of one udder half and TDM of the other half, enables the study of underlying mechanisms independently of inter-individual variability (same genetic background) and of environmental factors. Our results show that in first-calf heifers three CpG, located 10 kb upstream from the CSN1S1 gene were methylated to 33, 34 and 28%, respectively, after TDM but these levels were higher after ODM, 38, 38 and 33%, respectively. These methylation levels were much lower than those observed in the mammary gland during pregnancy (57, 59 and 50%, respectively) or in the liver (74, 78 and 61%, respectively). The methylation level of a fourth CpG (CpG4), located close by (29% during TDM) was not altered after ODM. CpG4 methylation reached 39.7% and 59.5%, during pregnancy or in the liver, respectively. CpG4 is located within a weak STAT5 binding element, arranged in tandem with a second high affinity STAT5 element. STAT5 binding is only marginally modulated by CpG4 methylation, but it may be altered by the methylation levels of the three other CpG nearby. Our results therefore shed light on mechanisms that help to explain how milk production is almost, but not fully, restored when TDM is resumed (15.1 ± 0.2 kg/day instead of 16.2 ± 0.2 kg/day, p<0.01). The STAT5 elements are 100 bp away from a region transcribed in the antisense orientation, in the mammary gland during lactation, but not during pregnancy or in other reproductive organs (ovary or testes). We now need to clarify whether the transcription of this novel RNA is a consequence of STAT5 interacting with the CSN1S1 distal region, or whether it plays a role in the chromatin structure of this region.
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Minh
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: INRA, UMR1348 Physiologie Environnement et Génétique pour l'Animal et les Systèmes d'Elevage, Saint-Gilles, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Boutinaud
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pétridou
authors.affiliation: INRA, UMR1198 Biologie du Développement et Reproduction, Jouy-en-Josas, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Gabory
authors.affiliation: INRA, UMR1198 Biologie du Développement et Reproduction, Jouy-en-Josas, France.
authors.forename: Maëlle
authors.initials: M
authors.lastname: Pannetier
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chat
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bouet
authors.affiliation: INRA, UMR1198 Biologie du Développement et Reproduction, Jouy-en-Josas, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Jouneau
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Jaffrezic
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Laloë
authors.affiliation: INRA, Sigenae, UR875 Biométrie et Intelligence Artificielle, Castanet-Tolosan, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Klopp
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Brun
authors.affiliation: INSERM U846 Stem Cell and Brain Research Institute, INRA, USC1361 AGROBIOSYSTEM, Université de Lyon 1 UMR S 846, Bron, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Kress
authors.affiliation: INRA, UMR1198 Biologie du Développement et Reproduction, Jouy-en-Josas, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Jammes
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Madia
authors.initials: M
authors.lastname: Charlier
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France.
authors.forename: Eve
authors.initials: E
authors.lastname: Devinoy
mesh_terms: D000818:Animals; D001483:Base Sequence; D002364:Caseins / Q000235:genetics*; D002417:Cattle; D019175:DNA Methylation; D003612:Dairying; D005260:Female; D007774:Lactation; D008321:Mammary Glands, Animal / Q000648:ultrastructure; D008892:Milk / Q000737:chemistry*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010446:Peptide Fragments / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D002364:Caseins; D010446:Peptide Fragments; C114674:alpha-casein (142-149)