Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the CYP17A1 missing in zona glomerulosa and thus produce the major glucocorticoid, cortisol. Zona fasciculata and zona reticularis cells also contain CYP17A1, whose 17,20-lyase activity is responsible for producing the androgens, dehydroepiandrosterone (DHEA) and androstenedione. Thus, fasciculata and reticularis cells can make corticosteroids and the adrenal androgens, but not aldosterone.
C 2 H 2 zinc finger domains (ZF) were classically identified as DBDs; however, recent work suggests a role in protein binding. For the purposes of this introductory chapter, we will briefly introduce how these proteins interact with XRSs. Recent estimates suggest that ∼3% of the human genome codes for C 2 H 2 zinc finger proteins (ZFPs). For multifinger proteins like the Wilms’ tumor suppressor transcription factor (WT1), only 3–4 ZFs are involved in DNA binding, leaving the other fingers to mediate other functions such as protein–protein interactions. The SP1 and early growth response 1 (EGR1) transcription factors use three ZFs motifs to mediate both DNA–protein and protein–protein binding ( Chapman and Perkins 2000; Seto et al. 1993 ). Of importance is that many ZFPs interact with XRSs to regulate function. Promyelocytic leukemia zinc finger (PLZF) protein is a known regulator of RARα, GR, and ERα. Kruppel-like factor 13 associates with CBP/p300, a known transcriptional partner in bHLH and NHR-induced gene activation ( McManus and Hendzel 2001 ). Work in the Ramos laboratory first established a link between environmental AHR ligands and deregulation of the WT1 ZFP resulting in nephrogenic deficits ( Falahatpisheh and Ramos 2003 ).
Engineered zinc finger arrays are often fused to a DNA cleavage domain (usually the cleavage domain of FokI ) to generate zinc finger nucleases . Such zinc finger-FokI fusions have become useful reagents for manipulating genomes of many higher organisms including Drosophila melanogaster , Caenorhabditis elegans , tobacco , corn ,  zebrafish ,  various types of mammalian cells,  and rats .  Targeting a double-strand break to a desired genomic locus can be used to introduce frame-shift mutations into the coding sequence of a gene due to the error-prone nature of the non-homologous DNA repair pathway. If a homologous DNA "donor sequence" is also used then the genomic locus can be converted to a defined sequence via the homology directed repair pathway. An ongoing clinical trial is evaluating Zinc finger nucleases that disrupt the CCR5 gene in CD4 + human T-cells as a potential treatment for HIV/AIDS .