title: Epigenetic regulation of the metallothionein-1A promoter by PU.1 during differentiation of THP-1 cells.
abstract: We recently demonstrated that metallothionein (MT)-1 A is a direct target gene negatively regulated by PU.1. In this study, we revealed that the expression of PU.1 was increased and accompanied by downregulation of MT-1A expression during TPA-induced THP-1 monocyte differentiation. Chromatin immunoprecipitation (ChIP) analysis demonstrated that PU.1 and the methyl CpG binding protein (MeCP) 2 bound to the same -887 to -602 region in the MT-1A promoter, and the binding of these proteins to this promoter was enhanced during differentiation. Consistently, bisulfite sequencing analyses around this region revealed that the proportion of methylated CpG sites was obivously increased during differentiation. In addition, ChIP analysis demonstrated that acetylated histone H4 around this region tended to be reduced and this may also play a role in the reduction of MT-1A expression during differentiation. Taken together, these findings suggest that MT-1A is epigenetically regulated by PU.1 during monocytic differentiation.
authors.affiliation: Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, Miniami-ku, Sagamihara, Kanagawa, Japan.
authors.forename: Sawami
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakano
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000187:drug effects; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D006657:Histones; D008668:Metallothionein; D011518:Proto-Oncogene Proteins; D013755:Tetradecanoylphorbol Acetate; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C530099:MT1A protein, human