Quantitative regulation of FLC via coordinated transcriptional initiation and elongation

• Published in: Proceedings of the National Academy of Sciences - PNAS 2016-01, Vol.113 (1), p.218-223
• Main Authors: Wu, Zhe, Ietswaart, Robert, Liu, Fuquan, Yang, Hongchun, Howard, Martin, Dean, Caroline
• Format: Article
• Language: English
• Subjects: Ambient temperature; Arabidopsis - genetics; Arabidopsis Proteins - genetics; Arabidopsis Proteins - metabolism; Arabidopsis thaliana; Biological Sciences; Chromatin; Chromatin - metabolism; Flowers & plants; Flowers - genetics; Gene expression; Gene Expression Regulation, Plant; Gene Silencing; Genetic Variation; Histone Deacetylases - metabolism; Histones - metabolism; MADS Domain Proteins - genetics; MADS Domain Proteins - metabolism; Mathematical models; Models, Genetic; Polyadenylation; RNA Folding; RNA polymerase; RNA Polymerase II - metabolism; RNA Splicing; RNA-Binding Proteins - metabolism; Transcription Elongation, Genetic; Transcription Initiation, Genetic
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1518369112

The basis of quantitative regulation of gene expression is still poorly understood. In Arabidopsis thaliana, quantitative variation in expression of FLOWERING LOCUS C (FLC) influences the timing of flowering. In ambient temperatures, FLC expression is quantitatively modulated by a chromatin silencing mechanism involving alternative polyadenylation of antisense transcripts. Investigation of this mechanism unexpectedly showed that RNA polymerase II (Pol II) occupancy changes at FLC did not reflect RNA fold changes. Mathematical modeling of these transcriptional dynamics predicted a tight coordination of transcriptional initiation and elongation. This prediction was validated by detailed measurements of total and chromatin-bound FLC intronic RNA, a methodology appropriate for analyzing elongation rate changes in a range of organisms. Transcription initiation was found to vary ∼25-fold with elongation rate varying ∼8- to 12-fold. Premature sense transcript termination contributed very little to expression differences. This quantitative variation in transcription was coincident with variation in H3K36me3 and H3K4me2 over the FLC gene body. We propose different chromatin states coordinately influence transcriptional initiation and elongation rates and that this coordination is likely to be a general feature of quantitative gene regulation in a chromatin context.