TY - JOUR T1 - <em>TCL1A</em>, a Novel Transcription Factor and a Coregulator of Nuclear Factor <em>κ</em>B p65: Single Nucleotide Polymorphism and Estrogen Dependence JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 700 LP - 710 DO - 10.1124/jpet.118.247718 VL - 365 IS - 3 AU - Ho, Ming-Fen AU - Lummertz da Rocha, Edroaldo AU - Zhang, Cheng AU - Ingle, James N. AU - Goss, Paul E. AU - Shepherd, Lois E. AU - Kubo, Michiaki AU - Wang, Liewei AU - Li, Hu AU - Weinshilboum, Richard M. Y1 - 2018/06/01 UR - http://jpet.aspetjournals.org/content/365/3/700.abstract N2 - T-cell leukemia 1A (TCL1A) single-nucleotide polymorphisms (SNPs) have been associated with aromatase inhibitor-induced musculoskeletal adverse events. We previously demonstrated that TCL1A is inducible by estradiol (E2) and plays a critical role in the regulation of cytokines, chemokines, and Toll-like receptors in a TCL1A SNP genotype and estrogen-dependent fashion. Furthermore, TCLIA SNP-dependent expression phenotypes can be “reversed” by exposure to selective estrogen receptor modulators such as 4-hydroxytamoxifen (4OH-TAM). The present study was designed to comprehensively characterize the role of TCL1A in transcriptional regulation across the genome by performing RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) assays with lymphoblastoid cell lines. RNA-seq identified 357 genes that were regulated in a TCL1A SNP- and E2-dependent fashion with expression patterns that were 4OH-TAM reversible. ChIP-seq for the same cells identified 57 TCL1A binding sites that could be regulated by E2 in a SNP-dependent fashion. Even more striking, nuclear factor-κB (NF-κB) p65 bound to those same DNA regions. In summary, TCL1A is a novel transcription factor with expression that is regulated in a SNP- and E2-dependent fashion—a pattern of expression that can be reversed by 4OH-TAM. Integrated RNA-seq and ChIP-seq results suggest that TCL1A also acts as a transcriptional coregulator with NF-κB p65, an important immune system transcription factor. ER -