Deciphering the epigenetic influence of a pro-neural transcription factor underlying neurogenesis

• Applicant: Privatdozent Dr. Vijay Tiwari
• Subject Area: General Genetics and Functional Genome Biology ; Developmental Neurobiology
• Term: from 2012 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 220387370

The cross-talk between transcription factors and epigenetic mechanisms in cell-fate specification during development has been increasingly appreciated. While a number of transcription factors have been implicated in controlling the onset, progression, and termination of neocortical neurogenesis, very little is known about their role in epigenetic reprogramming during this process. Our preliminary data suggest a pioneering transcription factor activity of an established proneural factor NeuroD1 and show that it reprograms chromatin and transcription factor landscapes to elicit gene expression program underlying neurogenesis. Building on these encouraging preliminary results, we want to achieve the following research aims within the proposed project: we will first identify genomewide targets of NeuroD1 and the impact of its binding on epigenetic landscape during neurogenesis in vivo (Aim 1). To gain understanding whether NeuroD1 has an impact on nuclear organization, we will analyze genomewide changes in chromatin long-range interactions following NeuroD1 binding at its target regulatory elements (Aim 2). We will next identify proteins that physically associate with NeuroD1 including transcription factors and epigenetic regulators and validate whether they play a role in NeuroD1's gene regulatory function (Aim 3). We will further employ computational tools to reveal genetic and epigenetic features that determine transcriptional responsiveness of NeuroD1 targeting to its binding sites (Aim 4). Next, we will implement systems biology approaches on all derived comprehensive datasets to model NeuroD1-dependent gene regulatory networks (Aim 5). Altogether, these findings will generate mechanistic models of how NeuroD1 impacts upon epigenome to elicit to the transcription program underlying neurogenesis.

• DFG Programme: Research Grants
• International Connection: United Kingdom