This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chong, S. Articles by Riggs, A. D. Search for Related Content PubMed PubMed Citation Articles by Chong, S. Articles by Riggs, A. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2002, p. 4667-4676, Vol. 22, No. 13
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.13.4667-4676.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Functional Chromatin Domain Does Not Resist X Chromosome Inactivation: Silencing of cLys Correlates with Methylation of a Dual Promoter-Replication Origin

Suyinn Chong,¹ Joanna Kontaraki,² Constanze Bonifer,² and Arthur D. Riggs^1*

Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010,¹ Molecular Medicine Unit, St. James' University Hospital, University of Leeds, Leeds LS9 7TF, United Kingdom²

Received 6 December 2001/ Returned for modification 13 February 2002/ Accepted 22 March 2002

To investigate the molecular mechanism(s) involved in the propagation and maintenance of X chromosome inactivation (XCI), the 21.4-kb chicken lysozyme (cLys) chromatin domain was inserted into the Hprt locus on the mouse X chromosome. The inserted fragment includes flanking matrix attachment regions (MARs), an origin of bidirectional replication (OBR), and all the cis-regulatory elements required for correct tissue-specific expression of cLys. It also contains a recently identified and widely expressed second gene, cGas41. The cLys domain is known to function as an autonomous unit resistant to chromosomal position effects, as evidenced by numerous transgenic mouse lines showing copy-number-dependent and development-specific expression of cLys in the myeloid lineage. We asked the questions whether this functional chromatin domain was resistant to XCI and whether the X inactivation signal could spread across an extended region of avian DNA. A generally useful method was devised to generate pure populations of macrophages with the transgene either on the active (Xa) or the inactive (Xi) chromosome. We found that (i) cLys and cGas41 are expressed normally from the Xa; (ii) the cLys chromatin domain, even when bracketed by MARs, is not resistant to XCI; (iii) transcription factors are excluded from lysozyme enhancers on the Xi; and (iv) inactivation correlates with methylation of a CpG island that is both an OBR and a promoter of the cGas41 gene.

---

* Corresponding author. Mailing address: Division of Biology, Beckman Research Institute of the City of Hope, 1500 East Duarte Rd., Duarte, CA 91010. Phone: (626) 301-8352. Fax: (626) 930-5366. E-mail: ariggs{at}coh.org.

---

Molecular and Cellular Biology, July 2002, p. 4667-4676, Vol. 22, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.13.4667-4676.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Li, N., Carrel, L. (2008). Escape from X chromosome inactivation is an intrinsic property of the Jarid1c locus. Proc. Natl. Acad. Sci. USA 105: 17055-17060 [Abstract] [Full Text]  
• Ciavatta, D., Kalantry, S., Magnuson, T., Smithies, O. (2006). A DNA insulator prevents repression of a targeted X-linked transgene but not its random or imprinted X inactivation. Proc. Natl. Acad. Sci. USA 103: 9958-9963 [Abstract] [Full Text]  
• Tagoh, H., Melnik, S., Lefevre, P., Chong, S., Riggs, A. D., Bonifer, C. (2004). Dynamic reorganization of chromatin structure and selective DNA demethylation prior to stable enhancer complex formation during differentiation of primary hematopoietic cells in vitro. Blood 103: 2950-2955 [Abstract] [Full Text]