Editors' ChoiceImmunology

PTIP in Immunoglobulin Switching

Science Signaling  24 Aug 2010:
Vol. 3, Issue 136, pp. ec260
DOI: 10.1126/scisignal.3136ec260

One of the hallmarks of humoral immunity is the ability of immunoglobulins (Igs) to undergo class switch recombination (CSR). Through genetic recombining of the Ig heavy chain, Igs maintain their antigen specificity but gain the ability to interact with different cell surface receptors required for successful pathogen clearance. CSR requires transcription at the Ig heavy-chain locus to initiate genetic rearrangement. Changes in chromatin accessibility are thought to promote CSR-associated transcription. Daniel et al. (see the Perspective by Singh and Demarco) now show that trimethylation of histone 3 at lysine 4 (H3K4me3) controls the accessibility of the Ig heavy-chain locus to CSR and that PTIP (Pax interaction with transcription-activation domain protein–1), a component of the histone methylase complex, is required for this modification. Mouse PTIP-deficient B cells exhibited impaired CSR. PTIP was required both for the recruitment of RNA polymerase II and for subsequent chromatin remodeling, including histone acetylation, which occurs during CSR. Largely independent of its function in transcription initiation in CSR, PTIP also associated with double-stranded DNA breaks during CSR and promoted genome stability. These dual functions of PTIP may be important for the precise coordination of chromatin accessibility and recombination required during CSR.

J. A. Daniel, M. A. Santos, Z. Wang, C. Zang, K. R. Schwab, M. Jankovic, D. Filsuf, H.-T. Chen, A. Gazumyan, A. Yamane, Y.-W. Cho, H.-W. Sun, K. Ge, W. Peng, M. C. Nussenzweig, R. Casellas, G. R. Dressler, K. Zhao, A. Nussenzweig, PTIP promotes chromatin changes critical for immunoglobulin class switch recombination. Science 329, 917–923 (2010). [Abstract] [Full Text]

H. Singh, I. A. Demarco, Double TIP-ping. Science 329, 914–915 (2010). [Summary] [Full Text]