TY - JOUR T1 - TCL1A, a novel transcription factor and a co-regulator of NF-кB p65: SNP and estrogen-dependence JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.118.247718 SP - jpet.118.247718 AU - Ming-Fen Ho AU - Edroaldo Lummertz da Rocha AU - Cheng Zhang AU - James Ingle AU - Paul Goss AU - Lois Shepherd AU - Michiaki Kubo AU - Liewei Wang AU - Hu Li AU - Richard Weinshilboum Y1 - 2018/01/01 UR - http://jpet.aspetjournals.org/content/early/2018/03/28/jpet.118.247718.abstract N2 - TCL1A single nucleotide polymorphisms (SNPs) have been associated with aromatase inhibitor-induced musculoskeletal adverse events. We previously demonstrated that TCL1A is estradiol (E2) inducible 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, e.g, 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-seq and 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, NF-кB 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 co-regulator with NF-кB p65, an important immune system transcription factor. ER -