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Abstract / Description of output
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.
Original language | English |
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Pages (from-to) | 2213-2220 |
Number of pages | 8 |
Journal | Cell Reports |
Volume | 24 |
Issue number | 9 |
DOIs | |
Publication status | Published - 28 Aug 2018 |
Keywords / Materials (for Non-textual outputs)
- MeCP2
- NLS
- Rett syndrome
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Core funding renewal for the Wellcome Trust Centre for Cell Biology
1/10/11 → 30/04/17
Project: Research
Profiles
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Adrian Bird
- School of Biological Sciences - Buchanan Chair of Genetics
- Edinburgh Neuroscience
- Centre for Engineering Biology
Person: Academic: Research Active