Figure 2. The structure of the Zbtb7b locus, illustrating important cis-acting elements.

The Zbtb7b locus encodes Th-POK (T-helper-inducing POZ/Kruppel-like factor). The Zbtb7b silencer (designated the distal response element; DRE⁴¹ or RUNX (runt-related transcription factor)-binding site 1 (RBS-1)⁴²) restricts the expression of Th-POK to MHC class II-specific thymocytes. The binding of RUNX to this region is necessary but not sufficient for silencer activity. The Zbtb7b silencer region also contains enhancer activity which, together with the general T-lymphoid element (GTE) may be involved in initiating the expression of Th-POK. The proximal enhancer (PE; also known as the proximal regulatory element (PRE)⁴¹ and/or RUNX- binding site 2 (RBS-2)^42,44) is not required to initiate the expression of Th-POK following positive selection, but is required to maintain Th-POK expression in MHC class II-selected thymocytes that are destined to become CD4⁺ T cells. Loss of the PE in the Zbtb7b locus leads to gradual loss of Th-POK expression and thereby causes partial redirection of MHC class II-selected thymocytes to the CD8 lineage. GATA3, GATA-binding protein 3.