The Feeney Lab

Welcome to the Feeney Lab!

Epigenetic, genetic and transcriptional control of B cell differentiation and B cell repertoire formation

A main focus of our lab is the molecular analysis of the epigenetic, genetic and transcriptional mechanisms which regulate accessibility of the V, D, and J immunoglobulin (Ig) gene segments for V(D)J recombination, and elucidation of the factors which influence the composition of the initial antibody repertoire. Although there are many V, D, and J genes at each locus, we have previously shown that different gene segments rearrange with quite different relative frequencies in pro-B cells in vivo. One of our goals is to understand the basis of this non-random gene utilization. We are analyzing the chromatin modifications that accompany B cell differentiation in vivo in an effort to understand the mechanism of lineage-specific and stage-specific control of accessibility of Ig genes.  3D-FISH is being used to study the changes in the 3-dimensional structure of the locus by transcription factors and by the CTCF/cohesin complex. A related issue is to determine which transcription factors control the changes in the epigenetic profile and in the 3-dimensional structure of the receptor loci at the developmental stage at which they undergo rearrangement. Current studies are aimed at elucidating the mechanism by which transcription factors control V(D)J rearrangement and B cell differentiation.