Skip to Content
MilliporeSigma
  • Evidence that TSC2 acts as a transcription factor and binds to and represses the promoter of Epiregulin.

Evidence that TSC2 acts as a transcription factor and binds to and represses the promoter of Epiregulin.

Nucleic acids research (2014-04-22)
Shalmali Avinash Pradhan, Mohammad Iqbal Rather, Ankana Tiwari, Vishwanath Kumble Bhat, Arun Kumar
ABSTRACT

The TSC2 gene, mutated in patients with tuberous sclerosis complex (TSC), encodes a 200 kDa protein TSC2 (tuberin). The importance of TSC2 in the regulation of cell growth and proliferation is irrefutable. TSC2 in complex with TSC1 negatively regulates the mTOR complex 1 (mTORC1) via RHEB in the PI3K-AKT-mTOR pathway and in turn regulates cell proliferation. It shows nuclear as well as cytoplasmic localization. However, its nuclear function remains elusive. In order to identify the nuclear function of TSC2, a whole-genome expression profiling of TSC2 overexpressing cells was performed, and the results showed differential regulation of 266 genes. Interestingly, transcription was found to be the most populated functional category. EREG (Epiregulin), a member of the epidermal growth factor family, was found to be the most downregulated gene in the microarray analysis. Previous reports have documented elevated levels of EREG in TSC lesions, making its regulatory aspects intriguing. Using the luciferase reporter, ChIP and EMSA techniques, we show that TSC2 binds to the EREG promoter between -352 bp and -303 bp and negatively regulates its expression. This is the first evidence for the role of TSC2 as a transcription factor and of TSC2 binding to the promoter of any gene.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phenylmethanesulfonyl fluoride, ≥98.5% (GC)
Sigma-Aldrich
PIPES, ≥99% (titration)
Sigma-Aldrich
Phenylmethanesulfonyl fluoride, ≥99.0% (T)
Sigma-Aldrich
PIPES, BioXtra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
Glycerol solution, 83.5-89.5% (T)
Sigma-Aldrich
Glycerol solution, puriss., meets analytical specification of Ph. Eur., BP, 84-88%
Sigma-Aldrich
PIPES, BioPerformance Certified, suitable for cell culture
Sigma-Aldrich
Rapamycin, Ready Made Solution, 2.5 mg/mL in DMSO (2.74 mM), from Streptomyces hygroscopicus
Sigma-Aldrich
PIPES, BioXtra, ≥99% (titration)
Sigma-Aldrich
PIPES, anhydrous, free-flowing, Redi-Dri, ≥99%
Sigma-Aldrich
Dimethyl sulfoxide, JIS special grade, ≥99.0%
Sigma-Aldrich
Ethylenediaminetetraacetic acid, SAJ special grade, ≥99.0%
Sigma-Aldrich
Dimethyl sulfoxide, SAJ first grade, ≥99.0%
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5%
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.0%, suitable for absorption spectrum analysis
Sigma-Aldrich
Dimethyl sulfoxide solution, 50 wt. % in H2O
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC
Supelco
Rapamycin, VETRANAL®, analytical standard
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)
Supelco
Dimethyl sulfoxide, analytical standard
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ≥98.0% (KT)
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture