Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis

Abstract

Spatiotemporal control of gene expression is central to animal development. Core promoters represent a previously unanticipated regulatory level by interacting with cis-regulatory elements and transcription initiation in different physiological and developmental contexts. Here, we provide a first and comprehensive description of the core promoter repertoire and its dynamic use during the development of a vertebrate embryo. By using cap analysis of gene expression (CAGE), we mapped transcription initiation events at single nucleotide resolution across 12 stages of zebrafish development. These CAGE-based transcriptome maps reveal genome-wide rules of core promoter usage, structure, and dynamics, key to understanding the control of gene regulation during vertebrate ontogeny. They revealed the existence of multiple classes of pervasive intra- and intergenic post-transcriptionally processed RNA products and their developmental dynamics. Among these RNAs, we report splice donor site-associated intronic RNA (sRNA) to be specific to genes of the splicing machinery. For the identification of conserved features, we compared the zebrafish data sets to the first CAGE promoter map of Tetraodon and the existing human CAGE data. We show that a number of features, such as promoter type, newly discovered promoter properties such as a specialized purine-rich initiator motif, as well as sRNAs and the genes in which they are detected, are conserved in mammalian and Tetraodon CAGE-defined promoter maps. The zebrafish developmental promoterome represents a powerful resource for studying developmental gene regulation and revealing promoter features shared across vertebrates.

Paired-End Analysis of Transcription Start Sites in Arabidopsis Reveals Plant-Specific Promoter Signatures

“…Cap-trapping protocols such as CAGE (Carninci et al, 2005) and PEAT (Ni et al, 2010) aim to isolate pol-II mRNA transcripts and sequence the capped ends (TSS tags) with nucleotide resolution. Recent analyses using genome-scale TSS data sets produced with PEAT and CAGE in animal tissues (Ni et al, 2010;Batut et al, 2013;Nepal et al, 2013) have observed that TSSs are not simply located at one or even a few "alternative start site" locations upstream of each pol-II gene. When these TSSs are mapped back to the genome, they distribute spatially in a variety of different "TSS tag clusters" or "initiation patterns."…”

Promoter architectures and developmental gene regulation

“…The function of these short and CAGE-sensitive RNAs mapping to internal exons and introns remains elusive. However, these RNA species arise only from a discrete subset of genes and their abundance often does not correlate with the expression of the host gene, arguing against them being merely degradation intermediates [37,38].…”

Decoding sORF translation – from small proteins to gene regulation

“…Lack of this 5'-most exon in differentiated myotubes could contribute to the increased Cryab protein production. 120,121 Because alternative TSS usage is common during vertebrate embryogenesis 122,123 and in different cell types, [124][125][126][127] such a transcription-based control of uORF regulation could have broad implications in developmental regulation of gene expression.…”