Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression.

摘要: Epigenetic modifications regulate developmental genes involved in stem cell identity and lineage choice. NFI-A is a posttranscriptional microRNA-223 (miR-223) target directing human hematopoietic progenitor decision: induction or silencing boosts erythropoiesis granulopoiesis, respectively. Here we show that promoter silencing, which allows guaranteed by epigenetic events, including the resolution of opposing chromatin "bivalent domains," hypermethylation, recruitment polycomb (PcG)-RNAi complexes, miR-223 targeting activity. During localizes inside nucleus targets region containing PcGs binding sites complementary DNA sequences, evolutionarily conserved mammalians. Remarkably, both integrity PcGs-RNAi complex sequences matching seed are required to induce transcriptional silencing. Moreover, ectopic expression myeloid progenitors causes heterochromatic repression gene channels whereas its stable knockdown produces opposite effects. Our findings indicate that, besides regulation translation mRNA targets, endogenous miRs can affect at level, functioning critical interface between remodeling complexes genome direct fate determination progenitors.