Figure 2. Model of lncRNA expression and chromatin organization of 15q11-13 during neuronal maturation.

In the immature neuron with multiple nucleoli and heterochromatic foci, both alleles are similarly compacted, the un-methylated paternal IC expresses Snrpn, while both alleles express Ube3a. During maturation the maternal allele remains compact, while the paternal allele decondenses. MeCP2, expressed at higher levels in neurons, co-localizes with heterochromatin and binds to the methylated maternal IC, localizing the maternal allele to heterochromatin and positioning it properly for increased Ube3a expression. At the same time, the paternal allele becomes highly active, expressing not only Snprn, but the snoRNA clusters and the antisense to Ube3a, blocking paternal Ube3a expression from the opposing strand. The snoRNAs are spliced from introns and processed into stem loops. The snoRNA transcript forms a lncRNA cloud possibly localized at the paternal allele which may recruit chromatin remodeling factors to the locus to drive paternal allele decondensation. The snoRNAs are ultimately transported to the nucleolus, increasing nucleolar size contributing to a mature neuronal nuclear phenotype of a single large nucleolus.