SULT1A1 is expressed in different tissues, in different physiological states of the same tissue, and in different individuals. The factors that regulate SULT1A1 gene expression are poorly understood. Human studies show that SULT1A1 can be regulated by alternative promoter usage , SNPs in the coding or promoter region [26, 27], CNVs , or variants in the 3′UTR of the gene . However, these genetic variants account for only a portion of the variation of SULT1A1 activity. Hempel et al.  identified Ets synergized with Sp1 as one of the regulators of SULT1A1 expression. It is postulated that ubiquitous Ets is utilized to ensure constant expression of SULT1A1 in tissues such as liver, skin, and gut, since SULT1A1 is important in xenobiotic metabolism. This current study elucidated NFI gene family as an important TF in regulating SULT1A1 expression in different cell types.
The data presented here suggest that NFI may play a major role in regulating SULT1A1 expression in different physiological and disease states. The NFI family proteins are associated with changes in different cell growth states and with oncogenic processes and disease states as reviewed in [33–35]. TF profiling array data demonstrated that NFI in high-SULT1A1-expressing ZR-75-1 breast cells was expressed more than in low-SULT1A1-expressing non-cancer MCF-10A cells. This positive association was also observed in human liver samples and in different human cell lines. Further siRNA transfection assays suggested that SULT1A1 expression is controlled, at least partially, by NFI in breast cancer cells. While the siRNA data demonstrate NFI-B has the least effect on SULT1A1 expression, there is still an effect and the p-value approached significance at p = 0.07, while the NFI isoforms with significant effects were at p = 0.05. This effect may not be a direct one, and NFI-B may not be the only factor which has an effect on SULT1A1 expression. Rather it may be part of another mechanism that has a compound effect on SULT1A1 expression. This could explain the lower significance of NFI-B. There was no additive SULT1A1 expression inhibition observed when ZR-75-1 cells were co-transfected with siNFI-A, siNFI-B, and siNFI-C, suggesting that each gene has its own role in regulating SULT1A1 expression.
NFI siRNA knockdown experiments inhibited about 40% of SULT1A1 expression in ZR-75-1 cells, suggesting other regulatory mechanism(s) exist. Previous studies have shown that the human population possesses one to five copies of SULT1A1, and that its enzyme activity is correlated with CNV [13, 14, 28]. The data presented here demonstrate that there were SULT1A1 copy number differences in human cell lines also, and that cells with more copies had higher SULT1A1 expression than cells with only one copy. However, higher copy number does not always correlate with the degree of expression. T-47D cells, which contained five copies, had similar SULT1A1 expression to that of ZR-75-1 cells, which contained three copies. MCF-7 and MDA-MB-231cells each contained one copy, yet MDA-MB-231 cells showed no SULT1A1 expression, while MCF-7 cells showed a modest amount of SULT1A1 expression. The data suggests that SULT1A1 gene expression could also be regulated by mechanisms other than NFI and copy numbers. SULT1A1 CNV in different cell lines reflect the range of SULT1A1 CNV reported in human populations [13, 14, 28]. Thus, cell lines could be used as a model for human SULT1A1 CNV-related studies.