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

Author:

Lunyak Victoria V.12345,Prefontaine Gratien G.12345,Núñez Esperanza12345,Cramer Thorsten12345,Ju Bong-Gun12345,Ohgi Kenneth A.12345,Hutt Kasey12345,Roy Rosa12345,García-Díaz Angel12345,Zhu Xiaoyan12345,Yung Yun12345,Montoliu Lluís12345,Glass Christopher K.12345,Rosenfeld Michael G.12345

Affiliation:

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.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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