Histone demethylase Jmjd3 is required for the development of subsets of retinal bipolar cells

Atsumi Iida, Toshiro Iwagawa, Hiroshi Kuribayashi, Shinya Satoh, Yujin Mochizuki, Yukihiro Baba, Hiromitsu Nakauchi, Takahisa Furukawa, Haruhiko Koseki, Akira Murakami, Sumiko Watanabe

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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 developmentwere 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.

Original languageEnglish
Pages (from-to)3751-3756
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number10
DOIs
Publication statusPublished - Mar 11 2014
Externally publishedYes

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Keywords

  • Histone methylation
  • Interneuron
  • Progenitor

ASJC Scopus subject areas

  • General

Cite this

Iida, A., Iwagawa, T., Kuribayashi, H., Satoh, S., Mochizuki, Y., Baba, Y., Nakauchi, H., Furukawa, T., Koseki, H., Murakami, A., & Watanabe, S. (2014). Histone demethylase Jmjd3 is required for the development of subsets of retinal bipolar cells. Proceedings of the National Academy of Sciences of the United States of America, 111(10), 3751-3756. https://doi.org/10.1073/pnas.1311480111