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RNA LEVER mediates long-range regulation of ε-globin by keeping PRC2 in check

ABSTRACT: EZH2, a core component of polycomb repressive complex 2 (PRC2), is a histone H3 methyltransferase required for gene silencing during embryonic development. The regulatory function of promiscuous binding of RNA to EZH2 is not known, although evidences suggest that binding of RNA inactivates EZH2 in vitro. Here we present a seesaw mechanism for the regulation of ε-globin through inactivating EZH2 by an upstream RNA (LEVER) in K562 cells. We show that LEVER, identified by RNA immune precipitation sequencing (RIP-seq) and NANOPORE sequencing, binds EZH2 and thereby preventing the accumulation of H3K27 methylation along the axis where LEVER emerges. The opened chromatin within LEVER in turn competes for the DNA looping between the locus control region (LCR) and the promoter of ε-globin. Hence, LEVER downregulates ε-globin by inhibiting EZH2.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141083 | GEO | 2022/02/15

REPOSITORIES: GEO

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RNA LEVER mediates long-range regulation of ε-globin by keeping PRC2 in check

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