title: Induction of endogenous interferon tau gene transcription by CDX2 and high acetylation in bovine nontrophoblast cells.
abstract: Interferon tau gene (IFNT) is expressed only by mononuclear trophectoderm cells in ruminant ungulates. To our knowledge, its epigenetic regulation and interaction with trophectoderm lineage-specific caudal-related homeobox 2 transcription factor (CDX2) have not been characterized. Herein, we studied differences in chromatin structures and transcription of endogenous bovine IFNT in bovine trophoblast BT-1 and CT-1 cells and in nontrophoblast MDBK cells. Transcripts from endogenous IFNT and CDX2 genes were found in BT-1 and CT-1 cells but not in MDBK cells. Chromatin immunoprecipitation study revealed that CDX2 binding sites exist in proximal upstream regions of IFNT (IFN-tau-c1). Endogenous IFNT transcription in BT-1 cells was increased with CDX2 overexpression but was reduced with short interfering RNA specific for the CDX2 transcript. In chromatin immunoprecipitation studies, histone H3K18 acetylation of IFNT was higher in CT-1 cells than in MDBK cells, while histone H3K9 methylation was lower in CT-1 cells than in nontrophoblast cells. In MDBK cells (but not in CT-1 cells), histone deacetylases were bound to IFNT, which was reversed with trichostatin A treatment; treatment with trichostatin A and CDX2 then increased IFNT mRNA levels that resulted from abundant CDX2 mRNA expression. These data provide evidence that significant increase in endogenous IFNT transcription in MDBK cells (which do not normally express IFNT) can be induced through CDX2 overexpression and high H3K18 acetylation, but lowering of H3K9 methylation could also be required for the degree of IFNT transcription seen in trophoblast cells.
authors.affiliation: Laboratory of Animal Breeding, Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakurai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Yoshikage
authors.initials: Y
authors.lastname: Muroi
authors.forename: Hanako
authors.initials: H
authors.lastname: Bai
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nagaoka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tamura
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hashizume
authors.forename: Miki
authors.initials: M
authors.lastname: Sakatani
authors.forename: Masashi
authors.initials: M
authors.lastname: Takahashi
authors.forename: James D
authors.initials: JD
authors.lastname: Godkin
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Imakawa
mesh_terms: D000107:Acetylation; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D006877:Hydroxamic Acids; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; D006877:Hydroxamic Acids; D007370:Interferon Type I; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C020947:interferon tau; C012589:trichostatin A; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases