GSE109909
Variable extent of lineage-specificity and developmental stage-specificity of cohesin and CTCF binding within the immunoglobulin and T cell receptor loci
The large antigen receptor (AgR) loci in T and B lymphocytes have many bound CTCF sites, most of which are only occupied in lymphocytes, while only the CTCF sites at the far end of each locus near enhancers or J genes tend to be bound in non-lymphoid cells also. However, despite the generalized lymphocyte restriction of CTCF binding in AgR loci, the Ig? locus is the only locus which also shows significant lineage-specificity (T vs. B cells) and developmental stage-specificity (pre-B, not pro-B) in CTCF binding. Cohesin is often bound at the same sites as CTCF, and cohesin is thought to create long range chromatin contacts by loop extrusion, with its translocation stopped by convergently oriented CTCF sites. Importantly, cohesin binding shows greater lineage- and stage- specificity than CTCF at most loci, thus providing more specificity to the CTCF/cohesin loops in AgR loci. Since all the CTCF sites within the large V portions of the Igh and TCRß loci have the same orientation, this suggests either a lack of requirement for convergent CTCF sites creating loops, or indicates an absence of any loops between CTCF sites within the V region portion of those loci but only loops to the convergent sites at the D-J-enhancer end of each locus. The V region portions of the Ig? and TCRa d loci, in contrast, have CTCF sites in both orientations, providing many options for creating CTCF-mediated loops throughout the loci. The immune system may have developed unique utilization of CTCF sites to generate lymphocyte-specific long-range loops to facilitate the formation of diverse antigen receptor repertoires. Overall design: For the ChIP-seq, input and immunoprecipitated DNA was given to the Next Generation Sequencing Core, where it was prepared for massively parallel sequencing on Illumina HiSeq2000.