Locus specific epigenetic modalities of random allelic expression imbalance

Genes are generally thought to be expressed from both alleles. There are some exceptions, including Random monoallelic expression (RME), even though its extent is still somewhat debated. We assessed whether and how some autosomal genes that we previously identified as being RME are prone to persistent and stable monoallelic expression. Not only do we confirm the occurrence of RME at large frequencies, our results also reveal unforeseen modes of allelic expression,that appear to be gene specific and epigenetically regulated. This non-canonical allelic regulation has large physiological and pathological implications and represents novel therapeutic perspectives. Overall design: Male or female hybrid (129sv x Castaneus) mouse ES cells were differentiated into NPCs, as previously described (PMID 16086633, 24576422). NPC clones were generated following manual colony picking after limited dilution of the NPC population. Clones were individually expanded and then harvested for RNA extraction. NPC clones were differentiated into astrocytes as previously described (PMID 24576422).