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Sharmilee Vetrivel, Jochen Graw, Florian Giesert; Identification of ocular regulatory functions of core histone variant H3.2 in mouse. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3435. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The posttranscriptional modifications (PTM) of the Histone H3 family play an important role in ocular system differentiation. For example, high levels of histone H3 K9 acetylation is needed for transcriptional activation of αA-crystallin during lens specification (Yang et al., 2006). However, there has been no study on the nature of specific Histone H3 subtype carrying these modifications. This lack of research challenges the recently developed epigenetic concept that structurally conserved mammalian histone H3 variants (H3.1, H3.2, and H3.3) exhibit distinct PTMs that influence epigenetic states during cellular differentiation and development (Hake & Allis 2006). Therefore, in the present study, the developmental role of Histone H3.2 have been characterized.
In this project, three strategies were employed to understand the unidentified roles of Histone H3.2.Real-time mRNA expression analysis of histone clusters in mouse embryonic development (emphasis on H3.2 gene clusters)Crispr cas approach was employed to produce a transgenic mouse line containing the fusion protein H3.2-GFP.Identification of binding sites of the H3.2 at different embryonic stages.
The real-time analysis found an increased expression of a specific histone H3.2 coding gene- Hist2h3c1 gene in the head region of the embryos. In addition, a coordinated regulation pattern was found among the Hist2 cluster genes during embryonic development. Transgenic mouse line containing the histone gene fused to GFP was established and characterized at genomic, transcriptional and protein level. The GFP tag was then used for ChIP Seq analysis of the DNA sequences bound by H3.2. The analysis revealed interesting ocular specific targets including BMP family genes, Pax6 and crystallins
This study identifies Hist2h3c1 encoded H3.2 as a key player in ocular development. By binding to specific regions of ocular developmental factors Histone H3.2 facilitates the function of these genes for successful lens & retina differentiation.References: Yang Y, Stopka T, Golestaneh N, Wang Y et al., Regulation of alpha-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin. EMBO J. 2006;25(10):2107-18.Hake SB, Allis CD. Histone H3 variants and their potential role in indexing mammalian genomes: the "H3 barcode hypothesis". Proc Natl Acad Sci U S A. 2006;103(17):6428-35
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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