TCL1A, a novel transcription factor and a coregulator of nuclear factor kB p65: Single nucleotide polymorphism and estrogen dependences

Ming Fen Ho, Edroaldo Lummertz da Rocha, Cheng Zhang, James N. Ingle, Paul E. Goss, Lois E. Shepherd, Michiaki Kubo, Liewei Wang, Hu Li, Richard M. Weinshilboum

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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-kB (NF-kB) 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-kB p65, an important immune system transcription factor.

Original languageEnglish
Pages (from-to)700-710
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume365
Issue number3
DOIs
Publication statusPublished - 01-06-2018

Fingerprint

T-Cell Leukemia
Single Nucleotide Polymorphism
Estrogens
Transcription Factors
RNA Sequence Analysis
Chromatin Immunoprecipitation
Selective Estrogen Receptor Modulators
Aromatase Inhibitors
Toll-Like Receptors
Chemokines
Estradiol
Immune System
Binding Sites
Genotype
Genome
Cytokines
Phenotype
Cell Line
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Ho, Ming Fen ; Lummertz da Rocha, Edroaldo ; Zhang, Cheng ; Ingle, James N. ; Goss, Paul E. ; Shepherd, Lois E. ; Kubo, Michiaki ; Wang, Liewei ; Li, Hu ; Weinshilboum, Richard M. / TCL1A, a novel transcription factor and a coregulator of nuclear factor kB p65 : Single nucleotide polymorphism and estrogen dependences. In: Journal of Pharmacology and Experimental Therapeutics. 2018 ; Vol. 365, No. 3. pp. 700-710.
@article{657dc819b5d14423a774623be6b55d12,
title = "TCL1A, a novel transcription factor and a coregulator of nuclear factor kB p65: Single nucleotide polymorphism and estrogen dependences",
abstract = "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-kB (NF-kB) 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-kB p65, an important immune system transcription factor.",
author = "Ho, {Ming Fen} and {Lummertz da Rocha}, Edroaldo and Cheng Zhang and Ingle, {James N.} and Goss, {Paul E.} and Shepherd, {Lois E.} and Michiaki Kubo and Liewei Wang and Hu Li and Weinshilboum, {Richard M.}",
year = "2018",
month = "6",
day = "1",
doi = "10.1124/jpet.118.247718",
language = "English",
volume = "365",
pages = "700--710",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TCL1A, a novel transcription factor and a coregulator of nuclear factor kB p65 : Single nucleotide polymorphism and estrogen dependences. / Ho, Ming Fen; Lummertz da Rocha, Edroaldo; Zhang, Cheng; Ingle, James N.; Goss, Paul E.; Shepherd, Lois E.; Kubo, Michiaki; Wang, Liewei; Li, Hu; Weinshilboum, Richard M.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 365, No. 3, 01.06.2018, p. 700-710.

Research output: Contribution to journalArticle

TY - JOUR

T1 - TCL1A, a novel transcription factor and a coregulator of nuclear factor kB p65

T2 - Single nucleotide polymorphism and estrogen dependences

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.

PY - 2018/6/1

Y1 - 2018/6/1

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-kB (NF-kB) 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-kB p65, an important immune system transcription factor.

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-kB (NF-kB) 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-kB p65, an important immune system transcription factor.

UR - http://www.scopus.com/inward/record.url?scp=85047213056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047213056&partnerID=8YFLogxK

U2 - 10.1124/jpet.118.247718

DO - 10.1124/jpet.118.247718

M3 - Article

AN - SCOPUS:85047213056

VL - 365

SP - 700

EP - 710

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -