ChIP-chip analysis of Ring1B in thymocytes

During ontogeny, totipotent progenitors undergo stepwise lineage-determination to give rise to progenitors with narrower potential and eventually to unipotent progenitors. Status of the progenitors with restricted potential is determined by transcription factors, and by epigenetic mechanisms. It is generally conceived that transcription factors primarily determine the commitment status of progenitors and epigenetic mechanisms follow to fix the status. In line with this idea is that, whereas many cases are known where the loss or over-expression of a certain single transcription factor bring about the cell fate conversion, no cases have ever been reported where alteration of epigenetic status solely leads to convert the determined cell lineage. Here we provide such a case where the inactivation of polycomb-medicated epigenetic regulation resulted in conversion of T lineage progenitors to B cell fate. In mice in which epigenetic repressor Ring1A and B are conditionally deleted in T cell lineage, T cell development was severely blocked at around T cell lineage determination step. Such developmental block was partially rescued by the additional deletion of Cdkn2a, one of cell cycle inhibitors, allowing the generation of T cell lineage progenitors that bear rearranged TCRβ chain gene. We found that these T cell progenitors co-express B cell lineage associated genes, and furthermore, these T cell progenitors were able to give rise to IgM+ mature B cells with normal function upon transfer to immuno-deficient mouse. These results indicate that T and B cell lineages are asymmetric in requirement of epigenetic regulation for the maintenance of respective lineages. ChIP samples of H3K4me3, H3K27me3 and Ring1B