FIG 8.
An Eμ bimodal activity model. This working model stipulates that Eμ activity shifts during early B cell development. (A) Prior to D-JH recombination, the Eμ enhancer controls sense and antisense transcription within the D-Cμ chromatin domain and sense transcription of a set of proximal VH gene segments that are more than 400 kb away. Eμ also controls D-JH recombination. Neither of the activities of the Eμ enhancer is hampered by either the IGCR1 CTCF/cohesin sites or the ectopic insulators. (B) After D-JH recombination, Eμ activity is focused on the nearby DJH promoter and becomes sensitive to the insulators' blocker effect. The control of DJH transcription is crucial for VH-DJH recombination and allelic exclusion. The arrows indicate only the sense and antisense transcripts which were shown to be controlled by the Eμ enhancer. The question marks mean that initiation and termination of the indicated antisense transcripts have not been unambiguously defined. The CpG of the JH1 segment is shown as a filled (methylated) or empty (unmethylated) lollipop. CBEs denote CTCF-binding elements within the intergenic control region (IGCR1) upstream of DFL16.1. The figure was compiled from information presented in references 12 to 18 and the present study.