title: Quantitative regulation of FLC via coordinated transcriptional initiation and elongation.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom;
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom; Computational and Systems Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Ietswaart
authors.affiliation: Department of Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom;
authors.forename: Fuquan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom;
authors.forename: Hongchun
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom; Computational and Systems Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom caroline.dean@jic.ac.uk martin.howard@jic.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Howard
authors.affiliation: Department of Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom; caroline.dean@jic.ac.uk martin.howard@jic.ac.uk.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dean
mesh_terms: D017360:Arabidopsis / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D035264:Flowers / Q000235:genetics; D018506:Gene Expression Regulation, Plant; D020868:Gene Silencing; D014644:Genetic Variation; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D026161:MADS Domain Proteins / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D026723:Polyadenylation; D059370:RNA Folding; D012319:RNA Polymerase II / Q000378:metabolism*; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000378:metabolism; D061805:Transcription Elongation, Genetic; D061785:Transcription Initiation, Genetic
chemical_list: D029681:Arabidopsis Proteins; D002843:Chromatin; C418902:At5g10140 protein, Arabidopsis; C106535:Flowering time control protein FCA, Arabidopsis; D006657:Histones; D026161:MADS Domain Proteins; D016601:RNA-Binding Proteins; D012319:RNA Polymerase II; C479923:flowering locus D protein, Arabidopsis; D006655:Histone Deacetylases
keywords: COOLAIR; FCA; alternative polyadenylation; autonomous pathway; chromatin