Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions
Abstract
While changes in MeCP2 dosage cause Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), its transcriptional regulation is poorly understood. Here, we identified six putative noncoding regulatory elements of Mecp2, 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 Mecp2/MECP2 and highlights genomic sites that could serve as diagnostic and therapeutic targets in RTT or MDS.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 18, 2021
- Source ID
- 10.1101/gad.345397.120
Entities
People
- Harini P. Tirumala
- Huda Y. Zoghbi
- Joshua D Wythe
- Manuel Cantu Gutierrez
- Sameer S. Bajikar
- Yingyao Shao
Organizations
- American Heart Association
- Canadian Institutes of Health Research
- Howard Hughes Medical Institute
- Intellectual and Developmental Disabilities Research Center
- National Institutes of Health
- United States Department of Defense