Relatively frequent switching of transcription start sites during cerebellar development

Peter Zhang,Winston Hide,Douglas J Swanson,Emmanuel Dimont,Thomas Ha,Dan Goldowitz

doi:10.1186/s12864-017-3834-z

Abstract

BackgroundAlternative transcription start site (TSS) usage plays important roles in transcriptional control of mammalian gene expression. The growing interest in alternative TSSs and their role in genome diversification spawned many single-gene studies on differential usages of tissue-specific or temporal-specific alternative TSSs. However, exploration of the switching usage of alternative TSS usage on a genomic level, especially in the central nervous system, is largely lacking.ResultsIn this study, We have prepared a unique set of time-course data for the developing cerebellum, as part of the FANTOM5 consortium (http://fantom.gsc.riken.jp/5/) that uses their innovative capturing of 5′ ends of all transcripts followed by Helicos next generation sequencing. We analyzed the usage of all transcription start sites (TSSs) at each time point during cerebellar development that provided information on multiple RNA isoforms that emerged from the same gene. We developed a mathematical method that systematically compares the expression of different TSSs of a gene to identify temporal crossover and non-crossover switching events. We identified 48,489 novel TSS switching events in 5433 genes during cerebellar development. This includes 9767 crossover TSS switching events in 1511 genes, where the dominant TSS shifts over time.ConclusionsWe observed a relatively high prevalence of TSS switching in cerebellar development where the resulting temporally-specific gene transcripts and protein products can play important regulatory and functional roles.

Highlights

Alternative transcription start site (TSS) usage plays important roles in transcriptional control of mammalian gene expression
Overview of promoter switch events during cerebellar development Our cerebellar time series, which consisted of transcriptome data from 12 time points, yielded a total of 183,903,557 Cap Analysis Gene Expression (CAGE) tags that are mapped to 25,207 genes in the reference genome
We identified 48,489 TSS switching events (Fig. 2a) in the cerebellar time series data that occur in 5433 genes

Summary

Introduction

Alternative transcription start site (TSS) usage plays important roles in transcriptional control of mammalian gene expression. Alternative splicing can provide a large reservoir of transcriptional variants from the ~22,000 genes identified by the Human Genome Project [1]. The production of different isoforms due to the usage of alternative transcription start sites (TSSs), which was once considered as uncommon, has been found in the majority of human genes [2, 3]. In the FANTOM project, CAGE has been shown to identify different TSSs and the corresponding promoters for single genes [6,7,8,9]. The understanding of how the TSS usage changes during development can shed light on how a single gene can function differently over developmental stages through temporally regulated alternative mRNA and protein isoforms

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Results

Conclusion