Identification and characterization of conserved noncoding -regulatory elements that impact expression and neurological functions.

While changes in MeCP2 dosage cause Rett syndrome (RTT) and duplication syndrome (MDS), its transcriptional regulation is poorly understood. Here, we identified six putative noncoding regulatory elements of , two of which are conserved in humans. Upon deletion in mice and human iPSC-derived neurons, these elements altered RNA and protein levels in opposite directions and resulted in a subset of RTT- and MDS-like behavioral deficits in mice. Our discovery provides insight into transcriptional regulation of and highlights genomic sites that could serve as diagnostic and therapeutic targets in RTT or MDS.