HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hodawadekar, S. Articles by Atchison, M. L. Search for Related Content PubMed PubMed Citation Articles by Hodawadekar, S. Articles by Atchison, M. L.

Epigenetic Histone Modifications Do Not Control Ig Locus Contraction and Intranuclear Localization in Cells with Dual B Cell-Macrophage Potential¹

Suchita Hodawadekar^*, Fang Wei^*, Duonan Yu, Andrei Thomas-Tikhonenko and Michael L. Atchison^2,*

^* Department of Animal Biology and Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104

Somatic rearrangement of the Ig genes during B cell development is believed to be controlled, at least in part, by accessibility of the loci to the recombinational machinery. Accessibility is poorly understood, but appears to be controlled by a combination of histone posttranslational modifications, large scale Ig locus contractions, and changes in intranuclear localization of the loci. These changes are regulated by developmental stage-specific as well as tissue-specific mechanisms. We previously isolated a murine B cell lymphoma line, Myc5, that can oscillate between the B cell and macrophage lineages depending upon growth conditions. This line provides an opportunity to study tissue-specific regulation of epigenetic mechanisms operating on the Ig loci. We found that when Myc5 cells are induced to differentiate from B cells into macrophages, expression of macrophage-specific transcripts was induced (M-CSFR, F4/80, and CD14), whereas B cell-specific transcripts decreased dramatically (mb-1, E47, IRF4, Pax5, and Ig). Loss of Ig transcription was associated with reduced Ig locus contraction, as well as increased association with heterochromatin protein-1 and association of the Ig locus with the nuclear periphery. Surprisingly, however, we found that histone modifications at the Ig locus remained largely unchanged whether the cells were grown in vivo as B cells, or in vitro as macrophages. These results mechanistically uncouple histone modifications at the Ig locus from changes in locus contraction and intranuclear localization.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants GM42415 (to M.L.A) and CA102709 (to A.T.-T.), plus support from the Commonwealth of Pennsylvania Health Research Formula Fund No. 4100020574 (to A.T.-T.).

² Address correspondence and reprint requests to Dr. Michael L. Atchison, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104. E-mail address: atchison{at}vet.upenn.edu

³ Abbreviations used in this paper: HP-1, heterochromatin protein-1; 3D-FISH, three-dimensional DNA fluorescence in situ hybridization; BAC, bacterial artificial chromosome; ChIP, chromatin immunoprecipitation; IRF, IFN regulatory factor.

This article has been cited by other articles:

				F. Wei, H. R. Scholer, and M. L. Atchison Sumoylation of Oct4 Enhances Its Stability, DNA Binding, and Transactivation J. Biol. Chem., July 20, 2007; 282(29): 21551 - 21560. [Abstract] [Full Text] [PDF]