title: Polycomb potentiates meis2 activation in midbrain by mediating interaction of the promoter with a tissue-specific enhancer.
abstract: Polycomb-group (PcG) proteins mediate repression of developmental regulators in a reversible manner, contributing to their spatiotemporally regulated expression. However, it is poorly understood how PcG-repressed genes are activated by developmental cues. Here, we used the mouse Meis2 gene as a model to identify a role of a tissue-specific enhancer in removing PcG from the promoter. Meis2 repression in early development depends on binding of RING1B, an essential E3 component of PcG, to its promoter, coupled with its association with another RING1B-binding site (RBS) at the 3' end of the Meis2 gene. During early midbrain development, a midbrain-specific enhancer (MBE) transiently associates with the promoter-RBS, forming a promoter-MBE-RBS tripartite interaction in a RING1-dependent manner. Subsequently, RING1B-bound RBS dissociates from the tripartite complex, leaving promoter-MBE engagement to activate Meis2 expression. This study therefore demonstrates that PcG and/or related factors play a role in Meis2 activation by regulating the topological transition of cis-regulatory elements.
authors.affiliation: Developmental Genetics Laboratory, RIKEN-IMS, Japan Science and Technology Agency, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; CREST, Japan Science and Technology Agency, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Kondo Research Unit, RIKEN-BSI, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: tkondo@rcai.riken.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Developmental Genetics Laboratory, RIKEN-IMS, Japan Science and Technology Agency, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Isono
authors.affiliation: Developmental Genetics Laboratory, RIKEN-IMS, Japan Science and Technology Agency, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; CREST, Japan Science and Technology Agency, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Kondo Research Unit, RIKEN-BSI, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Integrative Genomics Laboratory, RIKEN-IMS, Japan Science and Technology Agency, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Takaho A
authors.initials: TA
authors.lastname: Endo
authors.affiliation: Laboratory of Behavioral Genetics, RIKEN-BSI, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.affiliation: Centro de Investigaciones Biológicas, Department of Cellular and Molecular Biology, Ramiro de Maeztu 9, 28040 Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vidal
authors.affiliation: Developmental Genetics Laboratory, RIKEN-IMS, Japan Science and Technology Agency, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; CREST, Japan Science and Technology Agency, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Electronic address: koseki@rcai.riken.jp.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
mesh_terms: D000818:Animals; D001665:Binding Sites; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D063150:Polycomb Repressive Complex 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016548:Prosencephalon / Q000378:metabolism*; D011485:Protein Binding; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C102641:Mrg1 protein, mouse; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases