Dynamic Patterns of Histone Lysine Methylation in the Developing Retina

Rao, Rajesh C.; Tchedre, Kissaou; Malik, Maria; Coleman, Natasha; Fang, Yuan; Márquez, Víctor E.; Chen, Dong Feng

doi:10.1167/iovs.09-4730

Cited by 42 publications

(54 citation statements)

References 65 publications

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“…1D). Ezh2 is known to be highly expressed in the retina in the INBL at E16 but is undetectable in adult retina (19). RT-qPCR showed that the level of Ezh2 decreased after birth, and when retinal development was complete at about 2 wk after birth, Ezh2 expression was negligible (Fig.…”

Section: Significancementioning

confidence: 94%

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

Iida

Iwagawa

Kuribayashi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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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.histone methylation | progenitor | interneuron

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Section: Significancementioning

confidence: 94%

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

Iida

Iwagawa

Kuribayashi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…29 However, H3K9me2 has been implicated in the terminal commitment of blood, cardiac, retinal, neural, muscle and germline lineages. 23,25,29,[40][41][42][43] For example, H3K9me2 plays a dynamic role in retinal progenitor cells 44 and loss of Ehmt2 mediated epigenetic repression leads to profound defects in the early retina. Zebrafish ehmt2 morphants show severe decreases in crx, neuroD and irbp gene expression; markers of retinal cell differentiation.…”

Section: Canonical Roles Of Ehmt1/2 Complexmentioning

confidence: 99%

The expanding role of the Ehmt2/G9a complex in neurodevelopment

2017

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Epigenetic regulators play a crucial role in neurodevelopment. One such epigenetic complex, Ehmt1/2 (G9a/GLP), is essential for repressing gene transcription by methylating H3K9 in a highly tissue-and temporal-specific manner. Recently, data has emerged suggesting that this complex plays additional roles in regulating the activity of numerous other non-histone proteins. While much is known about the downstream effects of Ehmt1/2 function, evidence is only beginning to come to light suggesting the control of Ehmt1/2 function may be, at least in part, due to context-dependent binding partners. Here we review emerging roles for the Ehmt1/2 complex suggesting that it may play a much larger role than previously recognized, and discuss binding partners that we and others have recently characterized which act to coordinate its activity during early neurodevelopment.

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“…In order to identify possible patterns of HKM during retinal development, a recent study used a variety of methylated lysine-specific antibodies to probe retinal sections during different periods of murine retinogenesis [16]. An antibody against tri-methylated K4 of H3 (H3K4me3), an HKM mark associated with active gene transcription and euchromatin, was detected throughout the inner retina and outer retina during the proliferative phases of retinogenesis.…”

Section: Histone Methylation In Retinal Ganglion Cellsmentioning

confidence: 99%

“…Another report demonstrated the regulation of atonal homolog 5 (Ath5), a member of the basic helix-loop-helix [16,17] Present in all layers in adult murine retina [16], associated with transcription of ATH5 in newly born RGCs in chick retina [18].…”

Section: Histone Methylation In Retinal Ganglion Cellsmentioning

confidence: 99%

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Epigenetic regulation of retinal development and disease

Rao

Hennig

Malik

et al. 2011

j ocul biol dis inform

Self Cite

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Epigenetic regulation, including DNA methylation, histone modifications, and chromosomal organization, is emerging as a new layer of transcriptional regulation in retinal development and maintenance. Guided by intrinsic transcription factors and extrinsic signaling molecules, epigenetic regulation can activate and/or repress the expression of specific sets of genes, therefore playing an important role in retinal cell fate specification and terminal differentiation during development as well as maintaining cell function and survival in adults. Here, we review the major findings that have linked these mechanisms to the development and maintenance of retinal structure and function, with a focus on ganglion cells and photoreceptors. The mechanisms of epigenetic regulation are highly complex and vary among different cell types. Understanding the basic principles of these mechanisms and their regulatory pathways may provide new insight into the pathogenesis of retinal diseases associated with transcription dysregulation, and new therapeutic strategies for treatment.

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Dynamic Patterns of Histone Lysine Methylation in the Developing Retina

Cited by 42 publications

References 65 publications

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

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

The expanding role of the Ehmt2/G9a complex in neurodevelopment

Epigenetic regulation of retinal development and disease

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