title: Histone demethylase Jmjd3 is required for the development of subsets of retinal bipolar cells.
abstract: Di- and trimethylation of lysine 27 on histone H3 (H3K27me2/3) is an important gene repression mechanism. H3K27me2/3-specific demethylase, Jmjd3, was expressed in the inner nuclear layer during late retinal development. In contrast, H3K27 methyltransferase, Ezh2, was highly expressed in the embryonic retina but its expression decreased rapidly after birth. Jmjd3 loss of function in the developing retina resulted in failed differentiation of PKC-positive bipolar cell subsets (rod-ON-BP) and reduced transcription factor Bhlhb4 expression, which is critical for the differentiation of rod-ON-BP cells. Overexpression of Bhlhb4, but not of other BP cell-related genes, such as transcription factors Neurod and Chx10, in Jmjd3-knockdown retina rescued loss of PKC-positive BP cells. Populations of other retinal cell subsets were not significantly affected. In addition, proliferation activity and apoptotic cell number during retinal development were not affected by the loss of Jmjd3. Levels of histone H3 trimethyl Lys27 (H3K27me3) in the Bhlhb4 locus were lower in Islet-1-positive BP cells and amacrine cells than in the Islet-1-negative cell fraction. The Islet-1-negative cell fraction consisted mainly of photoreceptors, suggestive of lineage-specific demethylation of H3K27me3 in the Bhlhb4 locus. We propose that lineage-specific H3K27me3 demethylation of critical gene loci by spatiotemporal-specific Jmjd3 expression is required for appropriate maturation of retinal cells.
authors.affiliation: Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Atsumi
authors.initials: A
authors.lastname: Iida
authors.forename: Toshiro
authors.initials: T
authors.lastname: Iwagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuribayashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Satoh
authors.forename: Yujin
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Baba
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Sumiko
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000906:Antibodies; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D018274:Electroporation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008745:Methylation; D060888:Real-Time Polymerase Chain Reaction; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D000906:Antibodies; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D017931:DNA Primers; D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; C455509:Bhlhb4 protein, mouse; C524220:KDM6B protein, human
keywords: histone methylation; interneuron; progenitor