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Science 317 (5835): 248-251

Copyright © 2007 by the American Association for the Advancement of Science

Developmentally Regulated Activation of a SINE B2 Repeat as a Domain Boundary in Organogenesis

Victoria V. Lunyak,1,2* Gratien G. Prefontaine,1{dagger} Esperanza Núñez,1{dagger} Thorsten Cramer,5{dagger} Bong-Gun Ju,1 Kenneth A. Ohgi,1 Kasey Hutt,1 Rosa Roy,4 Angel García-Díaz,4 Xiaoyan Zhu,1 Yun Yung,1 Lluís Montoliu,4 Christopher K. Glass,3 Michael G. Rosenfeld1*

Abstract: The temporal and spatial regulation of gene expression in mammalian development is linked to the establishment of functional chromatin domains. Here, we report that tissue-specific transcription of a retrotransposon repeat in the murine growth hormone locus is required for gene activation. This repeat serves as a boundary to block the influence of repressive chromatin modifications. The repeat element is able to generate short, overlapping Pol II–and Pol III–driven transcripts, both of which are necessary and sufficient to enable a restructuring of the regulated locus into nuclear compartments. These data suggest that transcription of interspersed repetitive sequences may represent a developmental strategy for the establishment of functionally distinct domains within the mammalian genome to control gene activation.

1 Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, 9500 Gilman Drive, Room 345, La Jolla, CA 92093–0648, USA.
2 Department of Medicine, Division of Endocrinology, University of California, San Diego, La Jolla, CA 92093, USA.
3 Department of Cellular and Molecular Medicine, Department and School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
4 Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus de Cantoblanco, C/Darwin 3, 28049 Madrid, Spain.
5 Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.

{dagger} These authors contributed equally to this work.

* To whom correspondence should be addressed. E-mail: mrosenfeld{at} (M.G.R.); vlunyak{at} (V.V.L.)

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