PerspectiveGene Expression

Repeat after Me(CP2)!

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Science  25 Jun 2021:
Vol. 372, Issue 6549, pp. 1390-1391
DOI: 10.1126/science.abj5027

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Summary

Rett syndrome (RTT) is a devastating neurodevelopmental disease caused primarily by loss-of-function mutations in methyl-CpG-binding protein 2 (MECP2) (1). MeCP2 is a DNA binding protein (2) that controls gene expression, but the precise molecular mechanism by which MeCP2 loss drives RTT pathology remains unclear, partially because a distinct DNA motif that specifies MeCP2-DNA interactions is lacking. On page 1411 of this issue, Ibrahim et al. (3) demonstrate that MeCP2 binds modified cytosine in cytosine-adenine (CA) dinucleotide repeats, providing a new signature DNA motif for MeCP2 binding. MeCP2 protects CA repeats from high nucleosome occupancy, raising questions about the consequence of this binding on maintaining chromatin structure in neurons.

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