A unified model for yeast transcript definition

Abstract

Identifying genes in the genomic context is central to a cell's ability to interpret the genome. Yet, in general, the signals used to define eukaryotic genes are poorly described. Here, we derived simple classifiers that identify where transcription will initiate and terminate using nucleic acid sequence features detectable by the yeast cell, which we integrate into a Unified Model (UM) that models transcription as a whole. The cis-elements that denote where transcription initiates function primarily through nucleosome depletion, and, using a synthetic promoter system, we show that most of these elements are sufficient to initiate transcription in vivo. Hrp1 binding sites are the major characteristic of terminators; these binding sites are often clustered in terminator regions and can terminate transcription bidirectionally. The UM predicts global transcript structure by modeling transcription of the genome using a hidden Markov model whose emissions are the outputs of the initiation and termination classifiers. We validated the novel predictions of the UM with available RNA-seq data and tested it further by directly comparing the transcript structure predicted by the model to the transcription generated by the cell for synthetic DNA segments of random design. We show that the UM identifies transcription start sites more accurately than the initiation classifier alone, indicating that the relative arrangement of promoter and terminator elements influences their function. Our model presents a concrete description of how the cell defines transcript units, explains the existence of nongenic transcripts, and provides insight into genome evolution.

Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity

“…Enrichment and positional bias of TF motifs in promoters has been reported in several model species and human (FitzGerald et al, 2004; Lee et al, 2007; Marino-Ramirez et al, 2004; Ohler et al, 2002), and in some cases TFs appear to be involved in determining promoter identity (de Boer et al, 2014; Megraw et al, 2009). However, it is unknown whether this is a general property of eukaryotic promoters.…”

The Ground State and Evolution of Promoter Region Directionality

“…On the other hand, divergent transcription may be the byproduct of an open chromatin region, and thus represent transcriptional noise (de Boer et al, 2014; Seila et al, 2009; Struhl, 2007). At the heart of this debate lies the question of intrinsic directionality.…”

Small Genetic Circuits and MicroRNAs: Big Players in Polymerase II Transcriptional Control in Plants

“…The core site is the primary docking point of the Pol II preinitiation complex and historically has been described as a site within a region starting around 250 (i.e., 50 bases upstream of the TSS, also known as the +1 site) and ending around position +50 (i.e., 49 bases downstream of the +1 site) (Thomas and Chiang, 2006;Kadonaga, 2012;Kumari and Ware, 2013). Extensive studies in yeast, human, and Drosophila melanogaster early on identified CREs within the core promoter referred to as core promoter elements (CPEs) that are bound by basal or general transcription factors (Kadonaga, 2004(Kadonaga, , 2012Thomas and Chiang, 2006;de Boer et al, 2013) including TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH, with one of the most well defined and studied CPEs being the TATA box, which is bound by the TATA box binding protein component of TFIID. While these elements were initially thought to be universally present in Pol II gene promoters, it is now apparent that CPEs within the core promoter form a diverse set of CREs with no one CPE being identified universally (Kadonaga, 2004(Kadonaga, , 2012Thomas and Chiang, 2006;Kumari and Ware, 2013).…”