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Molecular and Cellular Biology, August 2006, p. 5569-5579, Vol. 26, No. 15
0270-7306/06/$08.00+0     doi:10.1128/MCB.00405-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Tissue-Specific Chromatin Modifications at a Multigene Locus Generate Asymmetric Transcriptional Interactions

Eung Jae Yoo,{dagger} Isabela Cajiao,{dagger},{ddagger} Jeong-Seon Kim,§,§ Atsushi P. Kimura, Aiwen Zhang,|| Nancy E. Cooke, and Stephen A. Liebhaber*

Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 8 March 2006/ Returned for modification 6 April 2006/ Accepted 20 May 2006

Random assortment within mammalian genomes juxtaposes genes with distinct expression profiles. This organization, along with the prevalence of long-range regulatory controls, generates a potential for aberrant transcriptional interactions. The human CD79b/GH locus contains six tightly linked genes with three mutually exclusive tissue specificities and interdigitated control elements. One consequence of this compact organization is that the pituitarycell-specific transcriptional events that activate hGH-N also trigger ectopic activation of CD79b. However, the B-cell-specific events that activate CD79b do not trigger reciprocal activation of hGH-N. Here we utilized DNase I hypersensitive site mapping, chromatin immunoprecipitation, and transgenic models to explore the basis for this asymmetric relationship. The results reveal tissue-specific patterns of chromatin structures and transcriptional controls at the CD79b/GH locus in B cells distinct from those in the pituitary gland and placenta. These three unique transcriptional environments suggest a set of corresponding gene expression pathways and transcriptional interactions that are likely to be found juxtaposed at multiple sites within the eukaryotic genome.

* Corresponding author. Mailing address: Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Blvd., 428 Clinical Research Building, Philadelphia, PA 19104. Phone: (215) 898-7834. Fax: (215) 573-5157. E-mail: liebhabe{at}mail.med.upenn.edu.

{dagger} These authors contributed equally to this work.

{ddagger} Present address: Children's Hospital of Pittsburgh, Pittsburgh, Pa.

§ Present address: Pennsylvania State University, University Park, Pa.

Present address: Hokkaido University, Sapporo, Japan.

|| Present address: Ohio State University, Columbus, Ohio.

Molecular and Cellular Biology, August 2006, p. 5569-5579, Vol. 26, No. 15
0270-7306/06/$08.00+0     doi:10.1128/MCB.00405-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kimura, A. P., Sizova, D., Handwerger, S., Cooke, N. E., Liebhaber, S. A. (2007). Epigenetic Activation of the Human Growth Hormone Gene Cluster during Placental Cytotrophoblast Differentiation. Mol. Cell. Biol. 27: 6555-6568 [Abstract] [Full Text]  


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