Elp1 histone acetyltransferase function regulates Myt1 transcription in sensory and sympathetic neur (2012)

Undergraduate: Swetha Pasala

Faculty Advisor: Yi Zhang
Department: Biology

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IKAP produces the Elp1 protein within the highly conserved elongator complex, which is implicated in histone acetyl transferase function in cells. Deficiency in the Elp1 protein results in Familial Dysautonomia, which inhibits the development and viability of sensory and sympathetic neurons. Here, we describe assays conducted to develop knockout mouse models and to elucidate the molecular phenotype of Elp1 deficiency. Histological sections indicated enlarged ventricles and high tissue loss in the telencephalon of the CKO cells. Stained CKO cells show a marked decrease in Map2 and CNPase levels, indicating an impaired differentiation of oligodendrocytes and neurons. Past studies have suggested that Elp1 is involved in the acetylation of alpha tubulin. However, western blots of –c wildtype and CKO cells showed no difference in alpha tubulin acetylation. A subsequent series of western blots indicated a downregulation of histone acetylation in CKO cells, and a microarray conducted on CKO and wildtype genomic DNA indicated differences in gene expression, and a marked downregulation of Myt1 expression. Chromatin Immunoprecipitation (ChIP) assay on Myt1 indicated a reduction of acetylated histones in CKO cells. From these data, we propose that Elp1 functions as an acetyltransferase which regulates the transcription of the Myt1 gene through acetylation of accessory histone proteins. The downregulation of Myt1 results in the aforementioned observed phenotype in Elp1 CKO cells.