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Transcriptional targeting by microRNA-Polycomb complexes: A novel route in cell fate determination

Volume 11, Issue 19   October 1, 2012
Pages 3543 - 3549
http://dx.doi.org/10.4161/cc.21468
Keywords: Polycomb complexes, chromatin remodeling, microRNA, microRNA-DNA interaction, transcriptional gene silencing
Authors: Giuseppe Zardo, Alberto Ciolfi, Laura Vian, Monia Billi, Serena Racanicchi, Francesco Grignani and Clara Nervi

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Abstract:
Advances in the understanding of the epigenetic events underlying the regulation of developmental genes expression and cell lineage commitment are revealing novel regulatory networks. These also involve distinct components of the epigenetic pathways, including chromatin histone modification, DNA methylation, repression by polycomb complexes and microRNAs. Changes in chromatin structure, DNA methylation status and microRNA expression levels represent flexible, reversible and heritable mechanisms for the maintenance of stem cell states and cell fate decisions. We recently provided novel evidence showing that microRNAs, besides determining the post-transcriptional gene silencing of their targets, also bind to evolutionarily conserved complementary genomic seed-matches present on target gene promoters. At these sites, microRNAs can function as a critical interface between chromatin remodeling complexes and the genome for transcriptional gene silencing. Here, we discuss our novel findings supporting a role of the transcriptional chromatin targeting by polycomb-microRNA complexes in lineage fate determination of human hematopoietic cells.

Received: June 15, 2012; Accepted: July 12, 2012; Published Online: August 16, 2012

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