Model for CTCF function at the Igh and Igκ loci. (A) CTCF binding at the IGCR1 in the V_H-D intergenic region in the Igh locus prevents inappropriate communication between the Igh enhancers and the proximal V_H gene segments. Targeted IGCR1 deletion in the mouse (right) leads to antisense transcription extending into proximal V_H segments of the V_H7381 family and concomitant aberrant rearrangement.^53,54  GLT indicates germline transcript; and IGCR1, intergenic control region 1. (B) Likewise, CTCF binding at the SIS element in the V_κ-J_κ intergenic region in the Igκ locus is important for proper germline transcription over the J_κ region, limits proximal Vκ recombination, and restricts κ enhancer interactions to the Igκ locus.^49,60  Conditional deletion of Ctcf in the mouse (right) leads to increased proximal V_κ3-family transcription and rearrangement, and increased expression of the neighboring Rpia gene (orange arrow). GLT indicates germline transcript; and SIS, silencer of intergenic sequence.