Identification of a novel epigenetic regulatory region within the pluripotency associated microRNA cluster, EEmiRC

The miR-290 cluster is expressed in embryonic stem cells (ESCs) and is important for the maintenance of pluripotency, but little is known about the mechanisms regulating the early embryonic microRNA cluster (EEmiRC) expression. Here we report the identification of a 332-bp intragenic enhancer (IE) able to modulate the transcription of the mouse EEmiRC locus, presumably through binding of transcription modulators like Oct3/4, Sox2 and CTCF. This IE also contains a CpG island showing a differential pattern of DNA and histone methylation marks during differentiation of ESCs, which places EEmiRC in a novel regulatory feedback loop with DNA methylases. Deletion of IE significantly reduced the transcription of the EEmiRC, further proving the importance of this region in regulating the expression of EEmiRC.