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Long nonoding RNAs in the X-inactivation center

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Abstract

The X-inactivation center is a hotbed of functional long noncoding RNAs in eutherian mammals. These RNAs are thought to help orchestrate the epigenetic transcriptional states of the two X-chromosomes in females as well as of the single X-chromosome in males. To balance X-linked gene expression between the sexes, females undergo transcriptional silencing of most genes on one of the two X-chromosomes in a process termed X-chromosome inactivation. While one X-chromosome is inactivated, the other X-chromosome remains active. Moreover, with a few notable exceptions, the originally established epigenetic transcriptional profiles of the two X-chromosomes is maintained as such through many rounds of cell division, essentially for the life of the organism. The stable and divergent transcriptional fates of the two X-chromosomes, despite residing in a shared nucleoplasm, make X-inactivation a paradigm of epigenetic transcriptional regulation. Originally proposed in 1961 by Mary Lyon, the X-inactivation hypothesis has been validated through much experimentation. In the last 25 years, the discovery and functional characterization has firmly established X-linked long noncoding RNAs as key players in choreographing X-chromosome inactivation.

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Abbreviations

ESCs:

Embryonic stem cells

Xist:

X-inactive specific transcript

PRC1:

Polycomb repressive complex 1

PRC2:

Polycomb repressive complex 2

H3-K27me3:

Histone H3 lysine 27 trimethylation

MSCI:

Meiotic sex chromosome inactivation

ORF:

Open reading frame

shRNA:

Short hairpin RNA

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Acknowledgments

The authors wish to thank members of the Kalantry lab for fruitful discussions. Work in the Kalantry lab is funded by the University of Michigan Endowment for the Basic Sciences, NIH, Ellison Medical Foundation, and the March of Dimes.

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Correspondence to Sundeep Kalantry.

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Responsible Editors: Brian P. Chadwick, Kristin C. Scott, and Beth A. Sullivan

Emily Maclary, Michael Hinten, and Clair Harris contributed equally to the manuscript.

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Maclary, E., Hinten, M., Harris, C. et al. Long nonoding RNAs in the X-inactivation center. Chromosome Res 21, 601–614 (2013). https://doi.org/10.1007/s10577-013-9396-2

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