Affinity for DNA Contributes to NLS Independent Nuclear Localization of MeCP2.

Matthew J Lyst, Robert Ekiert, Jacky Guy, Jim Selfridge, Martha V Koerner, Cara Merusi, Dina De Sousa, Adrian Bird

Cell reports 2018 Aug 28

filter terms:

MeCP2 is a nuclear protein that is mutated in the severe neurological disorder Rett syndrome (RTT). The ability to target β-galactosidase to the nucleus was previously used to identify a conserved nuclear localization signal (NLS) in MeCP2 that interacts with the nuclear import factors KPNA3 and KPNA4. Here, we report that nuclear localization of MeCP2 does not depend on its NLS. Instead, our data reveal that an intact methyl-CpG binding domain (MBD) is sufficient for nuclear localization, suggesting that MeCP2 can be retained in the nucleus by its affinity for DNA. Consistent with these findings, we demonstrate that disease progression in a mouse model of RTT is unaffected by an inactivating mutation in the NLS of MeCP2. Taken together, our work reveals an unexpected redundancy between functional domains of MeCP2 in targeting this protein to the nucleus, potentially explaining why NLS-inactivating mutations are rarely associated with disease. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Matthew J Lyst, Robert Ekiert, Jacky Guy, Jim Selfridge, Martha V Koerner, Cara Merusi, Dina De Sousa, Adrian Bird. Affinity for DNA Contributes to NLS Independent Nuclear Localization of MeCP2. Cell reports. 2018 Aug 28;24(9):2213-2220