MC-05 Does upregulation of miR-718 affect histone 3 (H3) modifications?
Abstract
Autism Spectrum Disorders (ASD), a broad group of neurodevelopmental disorders, have been increasing over the years, now affecting every 1 in 44 people. A clear cause has not been distinguished, however recently, studies have started to connect ASD and epigenetics, which are changes in gene expression that do not affect DNA sequences. Examples include DNA methylation, histone modifications, and micro-RNAs (miRNAs).
One such miRNA, miR-718, exists on the same transcript that overlaps with IRAK1, which is believed to be related to the progression of ASD when overexpressed. Presumably, miR-718 would be overexpressed in the brain, as well. We have preliminary data suggesting that miR-718 targets several enzymes that modify epigenetic factors. Therefore, we sought to investigate whether miR-718 affects histone modifications, specifically at histone 3. Histone 3 (H3) modification changes have been identified in ASD patients, and we intend to find a relationship between miR-718 and ASD.
We hypothesized that by increasing miR-718, there will be a downregulation of H3 modifications like histone 3 lysine 4 monomethylation (H3K4me1), histone 3 lysine 4 trimethylation (H3K4me3), and histone 3 lysine 9 acetylation (H3K9Ac) since this pattern is observed in patients with ASD. Notably, decreases in these 3 modifications leads to heterochromatin, which is when DNA is tightly wrapped around histones, which leads to a loss in genome-wide gene expression.
We investigated this by overexpressing miR-718 via RNA interference (RNAi) and using Epigentek histone modification array kits for H3 to detect changes in many different H3 modification types. Our findings may help further the research behind causes of ASD and help with discovery of better treatment for patients with ASD.
MC-05 Does upregulation of miR-718 affect histone 3 (H3) modifications?
Autism Spectrum Disorders (ASD), a broad group of neurodevelopmental disorders, have been increasing over the years, now affecting every 1 in 44 people. A clear cause has not been distinguished, however recently, studies have started to connect ASD and epigenetics, which are changes in gene expression that do not affect DNA sequences. Examples include DNA methylation, histone modifications, and micro-RNAs (miRNAs).
One such miRNA, miR-718, exists on the same transcript that overlaps with IRAK1, which is believed to be related to the progression of ASD when overexpressed. Presumably, miR-718 would be overexpressed in the brain, as well. We have preliminary data suggesting that miR-718 targets several enzymes that modify epigenetic factors. Therefore, we sought to investigate whether miR-718 affects histone modifications, specifically at histone 3. Histone 3 (H3) modification changes have been identified in ASD patients, and we intend to find a relationship between miR-718 and ASD.
We hypothesized that by increasing miR-718, there will be a downregulation of H3 modifications like histone 3 lysine 4 monomethylation (H3K4me1), histone 3 lysine 4 trimethylation (H3K4me3), and histone 3 lysine 9 acetylation (H3K9Ac) since this pattern is observed in patients with ASD. Notably, decreases in these 3 modifications leads to heterochromatin, which is when DNA is tightly wrapped around histones, which leads to a loss in genome-wide gene expression.
We investigated this by overexpressing miR-718 via RNA interference (RNAi) and using Epigentek histone modification array kits for H3 to detect changes in many different H3 modification types. Our findings may help further the research behind causes of ASD and help with discovery of better treatment for patients with ASD.