Transition of differential histone H3 methylation in photoreceptors and other retinal cells during retinal differentiation.

Kazuko Ueno,Toshiro Iwagawa,Yutaka Suzuki,Sumiko Watanabe,Hiroshi Kuribayashi,Yukihiro Baba,Hiromitsu Nakauchi,Akira Murakami,Masao Nagasaki

doi:10.1038/srep29264

Abstract

To analyze cell lineage-specific transitions in global transcriptional and epigenetic changes during retinogenesis, we purified retinal cells from normal mice during postnatal development into two fractions, namely, photoreceptors and other retinal cells, based on Cd73 expression, and performed RNA sequencing and ChIP sequencing of H3K27me3 and H3K4me3. Genes expressed in the photoreceptor lineage were marked with H3K4me3 in the Cd73-positive cell fraction; however, the level of H3K27me3 was very low in both Cd73-positive and -negative populations. H3K27me3 may be involved in spatio-temporal onset of a subset of bipolar-related genes. Subsets of genes expressed in amacrine and retinal ganglion cells, which are early-born retinal cell types, were suggested to be maintained in a silent state by H3K27me3 during late-stage retinogenesis. In the outer nuclear layer, upregulation of Rho and rod-related genes were observed in Ezh2-ablated retina, suggesting a role for H3K27me3 in the maintenance of proper expression levels. Taken together, our data on the transition of lineage-specific molecular signatures during development suggest that histone methylation is involved in retinal differentiation and maintenance through cell lineage-specific mechanisms.

Highlights

The vertebrate neural retina is organized into a laminar structure comprised of six types of neurons and glial cells, Müller glia, and astrocytes
Based on loss of function analyses of Ezh[2] and Jmjd[3], we reported that H3K27me[3] modification in Bhlhb[4] and Vsx[2] genes is critical for the maturation of PKC- and Recoverin-positive bipolar cell subsets[13,14]
We used P12 mouse retinas because at this stage, photoreceptors begin to degenerate in the mutant retina, and the expression of gene subsets in bipolar cells and photoreceptors, both of which differentiate during later stages of retinal development, is apparent

Summary

Introduction

The vertebrate neural retina is organized into a laminar structure comprised of six types of neurons and glial cells, Müller glia, and astrocytes. In the inner nuclear layer (INL), interneurons such as horizontal, amacrine, and bipolar cells are found in addition to the Müller glia cell body. In the mouse, these major retinal cell classes are generated from a common population of multipotent retinal progenitor cells between embryonic day (E) 11 and postnatal day (P) 10 in a conserved temporal order[1]. Previous studies examining the comprehensive genomic map using chromatin immunoprecipitation sequencing (ChIPseq) showed that genes expressed in mature rod photoreceptors have a unique signature of de novo H3K4me[2] accumulation[15]. We found that cell lineage- and genes-specific modifications of histones during retinal development

Methods

Results

Conclusion