The effect of histone post-translational modification on transcriptional bursting during development

标题：组蛋白翻译后修饰对发育过程中转录破裂的影响

Title: The effect of histone post-translational modification on transcriptional bursting during development In all eukaryotes studied, transcription at individual gene loci exhibits random oscillations between active and inactive states, a phenomenon known as transcription bursting, which fundamentally impacts the synchrony and robustness of cell fate specification during embryonic development. To understand how transcription controls development, it is necessary to uncover the molecular determinants that control the duration of bursts and the rates at which bursts occur. Eukaryotic transcription is requires chromatin remodelers to change the chromatin state at enhancers and promoters. It is unclear what effect chromatin remodeling has on transcription burst lengths and frequencies. Here, I will knock down an array of chromatin remodelers, histone methyltransferases, and histone acetylases during Drosophila oocyte development and determined their effect on early axis patterning. For those that effect patterning, I will determine how transcriptional burst lengths and frequencies are modified in target genes. I will identify target genes using RNA-seq and CHIP-seq. To querry changes in transcriptional bursting, I will employ single mRNA FISH and live nascent site imaging. To quantitatively describe state transitions using these assays, I will use a 2-state mathematical model of transcription states. Together, these experiments show how changes in chromatin states change transcriptional bursting dynamics in target genes. I am requesting an additional nine months to complete my work from June 1st, 2021 through March 31st, 2022.