PT - JOURNAL ARTICLE AU - Ming-Fen Ho AU - Edroaldo Lummertz da Rocha AU - Cheng Zhang AU - James N. Ingle AU - Paul E. Goss AU - Lois E. Shepherd AU - Michiaki Kubo AU - Liewei Wang AU - Hu Li AU - Richard M. Weinshilboum TI - <em>TCL1A</em>, a Novel Transcription Factor and a Coregulator of Nuclear Factor <em>κ</em>B p65: Single Nucleotide Polymorphism and Estrogen Dependence AID - 10.1124/jpet.118.247718 DP - 2018 Jun 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 700--710 VI - 365 IP - 3 4099 - http://jpet.aspetjournals.org/content/365/3/700.short 4100 - http://jpet.aspetjournals.org/content/365/3/700.full SO - J Pharmacol Exp Ther2018 Jun 01; 365 AB - 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.