Chromosome Activation

Reawakening your X

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Science  26 Jan 2018:
Vol. 359, Issue 6374, pp. 408
DOI: 10.1126/science.359.6374.408-c

X chromosome inactivation (XCI) ensures that only one X chromosome in a pair is expressed in a female somatic cell. A heterozygous X-linked mutation therefore affects about half of the somatic cells. In Rett syndrome, such a mutation in methyl-CpG–binding protein 2 (MECP2) causes motor and cognitive abnormalities. Carrette et al. identify a combination treatment that “reawakens” the silenced X chromosome, allowing production of normal MECP2 in cultured cells. Treatment involves an antisense oligonucleotide that blocks Xist, a noncoding RNA that facilitates XCI. When combined with a chemical inhibitor of DNA methylation (a modification that represses genes), MECP2 expression rose to 5% of the normal level, pointing to the therapeutic potential of partial X chromosome reactivation in the brain.

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1715124115 (2018).

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