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 Pawlitzky, I. Articles by Brodeur, P. H. Search for Related Content PubMed PubMed Citation Articles by Pawlitzky, I. Articles by Brodeur, P. H.

Identification of a Candidate Regulatory Element within the 5' Flanking Region of the Mouse Igh Locus Defined by Pro-B Cell-Specific Hypersensitivity Associated with Binding of PU.1, Pax5, and E2A¹

Inka Pawlitzky^*, Christina V. Angeles, Andrea M. Siegel, Michelle L. Stanton^*, Roy Riblet and Peter H. Brodeur^2,*,

^* Immunology Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111; Department of Pathology, Tufts University School of Medicine, Boston, MA 02111; and Torrey Pines Institute for Molecular Studies, San Diego, CA 92121

The Igh locus is controlled by cis-acting elements, including Eµ and the 3' IgH regulatory region which flank the C region genes within the well-studied 3' part of the locus. Although the presence of additional control elements has been postulated to regulate rearrangements of the V_H gene array that extends to the 5' end of the locus, the 5' border of Igh and its flanking region have not been characterized. To facilitate the analysis of this unexplored region and to identify potential novel control elements, we physically mapped the most D-distal V_H segments and scanned 46 kb of the immediate 5' flanking region for DNase I hypersensitive sites. Our studies revealed a cluster of hypersensitive sites 30 kb upstream of the most 5' V_H gene. Detection of one site, HS1, is restricted to pro-B cell lines and HS1 is accessible to restriction enzyme digestion exclusively in normal pro-B cells, the stage defined by actively rearranging Igh-V loci. Sequence motifs within HS1 for PU.1, Pax5, and E2A bind these proteins in vitro and these factors are recruited to HS1 sequence only in pro-B cells. Transient transfection assays indicate that the Pax5 binding site is required for the repression of transcriptional activity of HS1-containing constructs. Thus, our characterization of the region 5' of the V_H gene cluster demonstrated the presence of a single cluster of DNase I hypersensitive sites within the 5' flanking region, and identified a candidate Igh regulatory region defined by pro-B cell-specific hypersensitivity and interaction with factors implicated in regulating V(D)J recombination.

This article has been cited by other articles:

				D. J. Bolland, A. L. Wood, R. Afshar, K. Featherstone, E. M. Oltz, and A. E. Corcoran Antisense Intergenic Transcription Precedes Igh D-to-J Recombination and Is Controlled by the Intronic Enhancer E{micro} Mol. Cell. Biol., August 1, 2007; 27(15): 5523 - 5533. [Abstract] [Full Text] [PDF]

				H. Liu, M. Schmidt-Supprian, Y. Shi, E. Hobeika, N. Barteneva, H. Jumaa, R. Pelanda, M. Reth, J. Skok, K. Rajewsky, et al. Yin Yang 1 is a critical regulator of B-cell development Genes & Dev., May 15, 2007; 21(10): 1179 - 1189. [Abstract] [Full Text] [PDF]