Yin Yang 1 is a critical regulator of B-cell development
- Huifei Liu1,
- Marc Schmidt-Supprian1,2,
- Yujiang Shi1,7,
- Elias Hobeika3,
- Natasha Barteneva1,4,
- Hassan Jumaa3,
- Roberta Pelanda3,8,
- Michael Reth3,
- Jane Skok5,6,
- Klaus Rajewsky1,2, and
- Yang Shi1,9
- 1 Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 2 CBR Institute for Biomedical Research, Inc., Boston, Massachusetts 02115, USA;
- 3 Institute for Biology III, Albert-Ludwigs University of Freiburg and Max Planck Institute for Immunobiology, 79108 Freiburg, Germany;
- 4 Flow cytometry core facility, CBR Institute for Biomedical Research, Inc., Boston, Massachusetts 02115, USA;
- 5 Department of Immunology and Molecular Pathology, Division of Infection and Immunity, University College London, London W1T 4JF, United Kingdom
Abstract
The role of the transcription factor Yin Yang 1 (YY1) in development is largely unknown. Here we show that specific ablation of YY1 in mouse B cells caused a defect in somatic rearrangement in the immunoglobulin heavy-chain (IgH) locus and a block in the progenitor-B-to-precursor-B-cell transition, which was partially rescued by a prerearranged IgH transgene. Three-dimensional DNA fluorescence in situ hybridization analysis revealed an important function for YY1 in IgH locus contraction, a process indispensable for distal VH to DHJH recombination. We provide evidence that YY1 binds the intronic Eiμ enhancer within the IgH locus, consistent with a direct role for YY1 in VHDHJH recombination. These findings identified YY1 as a critical regulator of early B-cell development.
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Footnotes
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↵6 Present address: New York University School of Medicine, Department of Pathology, 550 1st Avenue, MSB531, New York, NY 10016, USA
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↵7 Endocrinology Division, Brigham and Women’s Hospital, Boston, MA 02115, USA;
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↵8 Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, 1400 Jackson Street, Denver, CO 80206, USA.
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↵9 Corresponding author.
↵9 E-MAIL yang_shi{at}hms.harvard.edu; FAX (617) 432-6687.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1529307
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- Received January 9, 2007.
- Accepted March 22, 2007.
- Copyright © 2007, Cold Spring Harbor Laboratory Press
