Pluto Bioinformatics

GSE109740: Transcription-associated histone pruning demarcates macroH2A chromatin domains

Bulk RNA sequencing

Here, we characterized de novo chromatin deposition of macroH2A2 using temporal genomic profiling in cells devoid of all macroH2A isoforms. We find that macroH2A2 is first pervasively deposited genome-wide and subsequently pruned to establish mature domains. This transient incorporation occurs preferentially at transcribed regions adjacent to future mature macroH2A2 domains and transcriptional inhibition prevents the clearing of promiscuously incorporated macroH2A2. Furthermore, CRISPR/Cas9-based manipulation of the transcriptional activity at a given locus reveals that transcriptional silencing triggers ectopic macroH2A2 accumulation, while activation depletes pre-existing macroH2A2. We demonstrate that the FACT (facilitates chromatin transcription) complex is required for macroH2A2 removal from transcribed chromatin. Taken together, we have identified a transcription-associated pruning mechanism that establishes and maintains the faithful genomic localization of macroH2A variants. SOURCE: Emily Bernstein (emily.bernstein@mssm.edu) - Bernstein Lab Mount Sinai School of Medicine