Proximal termination generates a transcriptional state that determines the rate of establishment of Polycomb silencing

• DOI: 10.1016/j.molcel.2024.05.014
• Publication Date: 2024-06-07T15:05:56Z
• Authors: Govind Menon; Eduardo Mateo-Bon...; Svenja Reeck; Robert Maple; Zhe Wu; Robert Ietswaart; Caroline Dean; Martin Howard
• Keywords: Polycomb-group proteins

The mechanisms and timescales controlling de novo establishment of chromatin-mediated transcriptional silencing by Polycomb repressive complex 2 (PRC2) are unclear. Here, we investigate PRC2 at Arabidopsis FLOWERING LOCUS C (FLC), known to involve co-transcriptional RNA processing, histone demethylation activity, function, but so far not mechanistically connected. We develop test a computational model describing proximal polyadenylation/termination mediated the RNA-binding protein FCA that induces H3K4me1 removal demethylase FLD. feeds back reduce polymerase II (RNA Pol II) processivity thus enhance early termination, thereby repressing productive transcription. predicts this transcription-coupled repression controls level antagonism action. Thus, effectiveness dictates timescale for PRC2/H3K27me3 silencing. experimentally validate these mechanistic predictions, revealing processing sets transcription locus, which then determines rate ON-to-OFF switch