Promoter architectures and developmental gene regulation

Abstract

Core promoters are minimal regions sufficient to direct accurate initiation of transcription and are crucial for regulation of gene expression. They are highly diverse in terms of associated core promoter motifs, underlying sequence composition and patterns of transcription initiation.Distinctive features of promoters are also seen at the chromatin level, including nucleosome positioning patterns and presence of specific histone modifications. Recent advances in identifying and characterizing promoters using next-generation sequencing-based technologies have provided the basis for their classification into functional groups and have shed light on their modes of regulation, with important implications for transcriptional regulation in development.This review discusses the methodology and the results of genome-wide studies that provided insight into the diversity of RNA polymerase II promoter architectures in vertebrates and other Metazoa, and the association of these architectures with distinct modes of regulation in embryonic development and differentiation.

The origins of developmental gene regulation

“…This postulate is supported by the regulatory features shared among promoters of developmental regulators and constitutive genes in yeast, vertebrates, long germ band insects, and plants (Basehoar et al 2004;Tirosh and Barkai 2008;Yamamoto et al 2009;Rach et al 2011;Lenhard et al 2012;Haberle and Lenhard 2016). This postulate is supported by the regulatory features shared among promoters of developmental regulators and constitutive genes in yeast, vertebrates, long germ band insects, and plants (Basehoar et al 2004;Tirosh and Barkai 2008;Yamamoto et al 2009;Rach et al 2011;Lenhard et al 2012;Haberle and Lenhard 2016).…”

“…In addition to the TATA box, other core promoter motives associate with narrow and broad TSSs, as summarized before (Juven-Gershon and Kadonaga 2010; Rach et al 2011;Lenhard et al 2012; M€ uller and Tora 2014). Structural features, such as the presence of a TATA box, broad TSS, and low variability of associated nucleosomes support the similarity of developmental promoters and constitutive promoters (Haberle and Lenhard, 2016). However, in metazoans, the SAGA-TBP interaction is weaker (Spedale et al 2012), and in humans, SAGA and its related complex ATAC (Spedale et al 2012) fail to show a preferential In the unicellular ancestor, the signal modulated transcription factor SM is constitutively expressed and binds transcriptional regulatory elements (TREs) of inducible gene I; in the absence of signal S, SM represses I, and in the presence of S, SM activates I transcription.…”

“…This postulate is supported by the regulatory features shared among promoters of developmental regulators and constitutive genes in yeast, vertebrates, long germ band insects, and plants (Basehoar et al 2004;Tirosh and Barkai 2008;Yamamoto et al 2009;Rach et al 2011;Lenhard et al 2012;Haberle and Lenhard 2016). 2 and 3) (Haberle and Lenhard 2016). Constitutive genes and developmental control genes usually have TATA-less proximal promoters, a nucleosome-free region flanked by invariably positioned nucleosomes containing histone variant H2A.Z, and a few transcription factors near their "broad" transcription start sites (TSSs), which have high variability in their site of transcription initiation (Figs.…”

“…Nucleosomes containing histone variants H3.3 and H2A.Z have higher DNA dissociation rates common to promoters and active CRMs in eukaryotes (Jin et al 2009; Arenas-Mena and Coffman 2015). H2A.Z nucleosomes facilitate the access of Pol II and transcription factors to the promoters of constitutively transcribed and developmentally regulated genes (Tirosh and Barkai 2008;Rach et al 2011;Haberle and Lenhard 2016), while access to the promoters of inducible and differentiation genes have to overcome more permanent nucleosomes (Weber and Henikoff 2014). Thus, canonical histone nucleosomes provide an additional mechanism to reduce the transcriptional noise of inducible and differentiation genes in the absence of activator inputs.…”

Core promoters across the genome

“…They have multiple, functionally distinct 1 and sometimes physically overlapping 2 architectures, which determine their responsiveness to long-range regulation and to developmental and differentiation regulatory programs (reviewed in ref. 3). …”