September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Varying Mitochondrial Haplogroups Show Differential Expression Levels of Histone Proteins
Author Affiliations & Notes
  • Jon Lucas Norman
    Gavin Herbert Eye Institute - UCI, Irvine, California, United States
  • Shari R Atilano
    Gavin Herbert Eye Institute - UCI, Irvine, California, United States
  • Marilyn Chwa
    Gavin Herbert Eye Institute - UCI, Irvine, California, United States
  • Kunal Thaker
    Gavin Herbert Eye Institute - UCI, Irvine, California, United States
  • Cristina M Kenney
    Gavin Herbert Eye Institute - UCI, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Jon Norman, None; Shari Atilano, None; Marilyn Chwa, None; Kunal Thaker, None; Cristina Kenney, None
  • Footnotes
    Support  Discovery Eye Foundation, Guenther Foundation, Beckman Initiative for Macular Research, Polly and Michael Smith Foundation, Max Factor Family Foundation, Iris and B. Gerald Cantor Foundation.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6053. doi:
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      Jon Lucas Norman, Shari R Atilano, Marilyn Chwa, Kunal Thaker, Cristina M Kenney; Varying Mitochondrial Haplogroups Show Differential Expression Levels of Histone Proteins. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6053.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Gene expression can be regulated by how tightly DNA associates with the nuclear proteins called histones, which are responsible for nucleosome structure integrity and gene regulation in eukaryotes. Recent studies show that cybrids (cytoplasmic hybrids), with identical nuclei but different mitochondrial (mt) DNA , differentially express methylation and acetylation genes. Our hypothesis is that different mtDNA haplogroups, representing populations from different geographic origins, have altered expression levels of histone proteins genes. The present study was conducted to determine if cybrids with mtDNA haplogroups H (European origin), L (African origin), and K (European origin – most common in Ashkenazi Jews) show differences in expression levels for histone genes.

Methods : Cybrids were created by fusing Rho0 ARPE-19 cells (devoid of mtDNA) with platelets isolated from Haplogroup H (n=8), L (n=6), or K (n=7) individuals. Haplogroups were determined by DNA analyses with PCR/restriction enzyme digestion and sequencing. Gene expression was analyzed by RT-qPCR for four histone genes using ALASv1 as a reference gene.

Results : L cybrids had lower expression levels for the histone genes HIST1H3F (2-fold, p=0.0003), HIST1H3H (0.44-fold, p=0.008), and HIST1H4H (0.63-fold, p=0.003) when compared to haplogroup H cybrids. K cybrids had lower expression levels for the histone genes HIST1H3A (0.3-fold, p<0.0001), HIST1H3H (0.28-fold, p<0.0001), and HIST1H4H (0.5-fold, p<0.0001) when compared to haplogroup H cybrids. The H cybrids values were assigned a value of 1.

Conclusions : Cybrids, which have identical nuclei but either H, L, or K haplogroup mtDNA, have differing RNA expression levels for histone genes. Previous studies have demonstrated that different mtDNA haplogroups mediate different expression levels of genes related to complement, inflammation, and apoptosis, but the mechanism(s) of retrograde signaling are not understood. Our results show that H, L and K cybrids also have unique expression levels of HIST1H3A, HIST1H3F, HIST1H3H and HIST1H4H, which would lead to variability in the nucleosome core and may influence acetylation/methylation status of cells and their retrograde signaling abilities. These factors may play a key role in gene regulation and in determining why cells from unique ethnic/racial origins are more susceptible to certain eye diseases.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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