title: DNA methylation and methyl-binding proteins control differential gene expression in distinct cortical areas of macaque monkey.
abstract: Distinct anatomical regions of the neocortex subserve different sensory modalities and neuronal integration functions, but mechanisms for these regional specializations remain elusive. Involvement of epigenetic mechanisms for such specialization through the spatiotemporal regulation of gene expression is an intriguing possibility. Here we examined whether epigenetic mechanisms might play a role in the selective gene expression in the association areas (AAs) and the primary visual cortex (V1) in macaque neocortex. By analyzing the two types of area-selective gene promoters that we previously identified, we found a striking difference of DNA methylation between these promoters, i.e., hypermethylation in AA-selective gene promoters and hypomethylation in V1-selective ones. Methylation levels of promoters of each area-selective gene showed no areal difference, but a specific methyl-binding protein (MBD4) was enriched in the AAs, in correspondence with expression patterns of AA-selective genes. MBD4 expression was mainly observed in neurons. MBD4 specifically bound to and activated the AA-selective genes both in vitro and in vivo. Our results demonstrate that methylation in the promoters and specific methyl-binding proteins play an important role in the area-selective gene expression profiles in the primate neocortex.
authors: Division of Brain Biology, National Institute for Basic Biology, Okazaki, Aichi 444-8585, Japan, Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan, Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan, and The Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa 240-0193, Japan.
authors: Katsusuke
authors: K
authors: Hata
authors: Hiroaki
authors: H
authors: Mizukami
authors: Osamu
authors: O
authors: Sadakane
authors: Akiya
authors: A
authors: Watakabe
authors: Masanari
authors: M
authors: Ohtsuka
authors: Masafumi
authors: M
authors: Takaji
authors: Masaharu
authors: M
authors: Kinoshita
authors: Tadashi
authors: T
authors: Isa
authors: Keiya
authors: K
authors: Ozawa
authors: Tetsuo
authors: T
authors: Yamamori
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D019175:DNA Methylation; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D004706:Endodeoxyribonucleases