College of Arts & Sciences

Nihar Desai

College of Arts & Sciences Biological Sciences

Mentor:

Effect of reduced HDAC 1, 3 on Kismet knockdown animals

CHARGE Syndrome is a neurodevelopmental disorder caused by haploinsufficiency of the Chromatin Helicase DNA (CHD) binding 7 gene. CHD7 is an epigenetic reader that is associated with the activation of gene expression. Our lab has previously shown that reduction of the Drosophila homologue of CHD7, Kismet (Kis), can lead to many neuroanatomical and motor function defects. Histone deacetylases (HDACs) are chromatin modifiers that remove acetyl groups to reduce gene expression by strengthening histone-DNA interactions. Pharmacological inhibition of HDACs has been shown to reduce such defects. We hypothesized that using RNA interference (RNAi) can recapitulate these results. The focus of our study was on HDAC1 and HDAC3, which are involved in several late-onset genetic neurodegenerative disorders. We expressed either a HDAC RNAi alone or with Kis RNAi in the fly and performed behavioral assays to observe changes in phenotype. When HDAC1 was knocked down, significant decreases in larval locomotor behavior were observed while knockdown of HDAC3 showed no significant change. When RNAis were coexpressed in the same fly, larval locomotor defects were rescued as compared to Kis RNAi alone.