| Popis: |
Immunoglobulin heavy chain (IgH) expression and Ig secretion is inhibited by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD). Within the IgH gene, the 3' IgH regulatory region (3'IgH RR) has been identified as a transcriptional target of TCDD. The 3'IgH RR, which in part regulates transcription of the IgH gene, is composed of four enhancers in the mouse: hs3a; hs1,2; h3b; hs4 and three enhancers in the human: hs3a; hs1,2; hs4. In humans the hs1,2 enhancer has an invariant sequence (IS) containing a DRE, NF-κB, NF1 and AP-1 binding site. Also, the enhancer has an AP1.ETS and Oct site located 5' to the IS. The human hs1,2 enhancer is sensitive to TCDD-induced modulation but in contrast to the mouse hs1,2 and 3'IgH RR, TCDD activates the human hs1,2 enhancer. The current study demonstrates the complexity of how TCDD differentially induces modulation between mouse and human and what role these binding sites may have. |
