Abstract

Modifications of histones are reportedly associated with the regulation of immunoglobulin (Ig) gene diversification mechanisms, but the extent of their involvement in promoting sequence alterations at the Ig variable (V) regions still remains to be elucidated. We have previously demonstrated that Ig gene conversion in the B cell line DT40 is accompanied by the local hyperacetylation of histones, and that its frequency is highly increased in cells treated with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA). In this report, we describe the enhancing effects of the homozygous deletion of HDAC2 (HDAC2-/-) on Ig gene conversion. Remarkably, sequence analysis revealed that the distribution of the gene conversion tracts induced throughout the Ig V regions in HDAC2-/- was significantly different from the diversification patterns in TSA-treated wild-type cultures. Furthermore, we found that the effects of HDAC2-/- and of the treatment with TSA were additive as regards histone acetylation, Ig gene transcription, gene conversion frequency and distribution of gene conversion tracts. These results underscore the potential participation of HDAC-mediated histone acetylation in Ig diversification, but also suggest a specific role of HDAC2 to control the spatial targeting of Ig gene conversion.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.