H2AK121ub in Arabidopsis associates with a less accessible chromatin state at transcriptional regulation hotspots

Abstract

Although it is well established that the Polycomb Group (PcG) complexes maintain gene repression through the incorporation of H2AK121ub and H3K27me3, little is known about the effect of these modifications on chromatin accessibility, which is fundamental to understand PcG function. Here, by integrating chromatin accessibility, histone marks and expression analyses in different Arabidopsis PcG mutants, we show that PcG function regulates chromatin accessibility. We find that H2AK121ub is associated with a less accessible but still permissive chromatin at transcriptional regulation hotspots. Accessibility is further reduced by EMF1 acting in collaboration with PRC2 activity. Consequently, H2AK121ub/H3K27me3 marks are linked to inaccessible although responsive chromatin. In contrast, only-H3K27me3-marked chromatin is less responsive, indicating that H2AK121ub-marked hotspots are required for transcriptional responses. Nevertheless, despite the loss of PcG activities leads to increased chromatin accessibility, this is not necessarily accompanied by transcriptional activation, indicating that accessible chromatin is not always predictive of gene expression.

Enhanced Autolysosomal Function Ameliorates the Inflammatory Response Mediated by the NLRP3 Inflammasome in Alzheimer’s Disease

“…We found that the protein expression level of LC3 was increased. This finding is consistent with previous studies (François et al, 2015;Alvarez-Arellano et al, 2018). LC3 is a universal biochemical index for observing autophagy and assessing autophagic activity.…”

“…In this study, NLRP3, caspase-1, and IL-1β were increased in the brain tissues of the AD model mice, which was consistent with previous research results (François et al, 2014). In in vitro experiments, NLRP3, caspase-1, and IL-1β were increased in BV2 cells.…”

“…Alzheimer's disease (AD), the most common type of dementia, is a neurodegenerative disease with cognitive impairment as the primary clinical manifestation (Ahmed et al, 2017;Teimouri et al, 2020). Central inflammatory reactions are involved in the pathological process of AD, and microglia and many molecular mediators participate in the inflammatory response (François et al, 2014). Glial cells aggregate near senile plaques in the brains of AD patients and experimental rats (Son et al, 2012), and these structures may be related to the activation of inflammatory bodies by aggregating amyloid proteins and misfolded proteins (Masters and O'Neill, 2011).…”

“…The inflammatory response, with the NLRP3 inflammasome as the core, is an important part of the neuroimmune response (You et al, 2017;La Rosa et al, 2019). Studies have found that high levels of toxic Aβ aggregation may induce the activation of the NLRP3 inflammasome, mediate harmful chronic inflammatory reactions, and promote the progression of AD (François et al, 2014).…”

Dynamics of H3K27me3 Modification on Plant Adaptation to Environmental Cues

“…The canonical hierarchical model proposed that PRC2-mediated H3K27me3 does not intrinsically impact the chromatin structure but serves as a docking site for PRC1 complex [63]. PRC1 in turn catalyzes the mono-ubiquitination of histone H2A (H2Aub), thus preventing the recruitment of nucleosome remodeling factors and subsequent gene silencing (Figure 1C) [63][64][65][66][67]. In line with this notion, genome-wide chromatin binding profiles demonstrated co-occupancy of PRC1 and PRC2 at many H3K27me3 deposition loci from animals to plants [9,[67][68][69][70][71][72][73].…”