Chromatin-based mechanisms to coordinate convergent overlapping transcription

Abstract

In eukaryotic genomes, the transcription units of genes often overlap with other protein-coding and/or noncoding transcription units^1,2. In such intertwined genomes, the coordinated transcription of nearby or overlapping genes would be important to ensure the integrity of genome function^3-6; however, the mechanisms underlying this coordination are largely unknown. Here, we show in Arabidopsis thaliana that genes with convergent orientation of transcription are major sources of antisense transcripts and that these genes transcribed on both strands are regulated by a putative Lysine-Specific Demethylase 1 family histone demethylase, FLOWERING LOCUS D (FLD)^7,8. Our genome-wide chromatin profiling revealed that FLD, as well as its associating factor LUMINIDEPENDENS⁹, downregulates histone H3K4me1 in regions with convergent overlapping transcription. FLD localizes to actively transcribed genes, where it colocalizes with elongating RNA polymerase II phosphorylated at the Ser2 or Ser5 sites. Genome-wide transcription analyses suggest that FLD-mediated H3K4me1 removal negatively regulates the transcription of genes with high levels of antisense transcription. Furthermore, the effect of FLD on transcription dynamics is antagonized by DNA topoisomerase I. Our study reveals chromatin-based mechanisms to cope with overlapping transcription, which may occur by modulating DNA topology. This global mechanism to cope with overlapping transcription could be co-opted for specific epigenetic processes, such as cellular memory of responses to the environment¹⁰.