*2.2.9.1 Transcription-sequential/ordered model-of germinal loci and accessibility by RAG-1 and RAG-2 proteins*

It should be clearly noted that the VH segments are not silent before the V-DJH recombination steps or before their physical juxtaposition with the Eμ enhancer. It has therefore been shown that they undergo active noncoding germline transcription in B-cell precursors. In addition, many other noncoding transcripts appear as rearrangements occur, in order to allow the opening of chromatin, and thus, the targeting and accessibility by RAG-1/RAG-2 complex, as well as the establishment of the three-dimensional structure of the locus considered. From a kinetic point of view, the first noncoding DH transcripts, also referred to as sterile transcripts (to differentiate them from the coding transcripts, which are initiated at the rearranged VDJ segments), are detected before the D-JH rearrangements and are initiated at JH-proximal DH gene (DQ52), which has both promoter and enhancer activities preferentially active in B-cell precursors [20], generating μ0 transcripts, and at downstream of intronic IGH enhancer Eμ, generating Iμ transcripts. Both μ0 and transcripts Iμ are getting spliced and polyadenylated [ 21]. Once the DJH rearrangement is carried out, new noncoding germinal transcripts appear in VH regions (for review, see [21]).
