FIGURE 1.2.
Transcripts within the IgH locus. VH, DH, JH gene segments and CH exons are shown as rectangles, enhancer and promoter elements as ovals. 12 bp and 23 bp RSSs are depicted as black and white triangles, respectively. Drawings not to scale. (A) The IgH locus in germline configuration is transcribed from the promoter of DQ52 (PDQ52) to produce the μ0 transcript (Alessandrini and Desiderio, 1991), and from within the Eμ enhancer to generate the Iμ transcript (Lennon and Perry, 1985; Su and Kadesch, 1990), both of which are getting spliced and polyadenylated (Kottmann et al., 1994, Su and Kadesch, 1990). DH and JH elements are transcribed in the antisense orientation (Bolland et al., 2007; Chakraborty et al., 2007), suggested start sites (dashed arrows) are located around PDQ52 (Chakraborty et al., 2007) and Eμ (Bolland et al., 2007). Sites of transcriptional termination of DH–JH antisense germline transcripts are unknown. (B) Unrearranged VH segments are transcribed in the sense orientation from the individual VH promoters (VHP) (Yancopoulos and Alt, 1985). The intron between the leader (L) and the VH exon (VH) is spliced out, and the VH sense germline transcript gets polyadenylated (Yancopoulos and Alt, 1985). The VH segments and VH intergenic regions can also get transcribed in the antisense orientation (Bolland et al., 2004). Start and termination sites of VH antisense germline transcripts are unknown. Therefore, individual antisense transcripts could comprise one VH segment and its adjacent regions or multiple VH segments including intergenic regions, shown as short and long solid arrows, respectively. (C) Upon D to JH recombination, the assembled DJH exon gets transcribed from the DH promoter (PDH) and spliced to the Cμ exons to generate the Dμ transcript (Alessandrini and Desiderio, 1991; Reth and Alt, 1984), which in one reading frame encodes for a short μHC molecule (Reth and Alt, 1984). DH antisense germline transcription is present throughout the remaining unrearranged DH segments (Chakraborty et al., 2007). Suggested origin of DH antisense germline transcripts is the region around the promoter of the recombined DH segment (depicted as PDH) (Chakraborty et al., 2007), transcriptional termination sites are unknown. (D) Upon VH to DJH recombination, the promoter of the rearranged VH segment (depicted as VHP) drives expression of mRNA encoding for the μHC. In addition to Iμ sense transcription, the Sμ switch region is also transcribed in the antisense orientation (Perlot et al., 2008) from promoters residing within Sμ (Apel et al., 1992; Morrison et al., 1998), the transcriptional termination site of the Sμ antisense transcript is unknown. The assembled VHDJH exon and the adjacent JH region are transcribed in the antisense orientation potentially from start sites within the JH cluster (dashed arrow) (Perlot et al., 2008), the transcriptional termination site of the VHDJH antisense transcript is unknown. Upstream unrearranged VH segments are transcriptionally silenced upon assembly of a functional VHDJH exon (Bolland et al., 2004; Yancopoulos and Alt, 1985).