The application notes include recommended starting dilutions; optimal dilutions/concentrations should be determined by the end user.
Application notesWB: Use at a concentration of 1-5 µg/ml.
Not yet tested in other applications. Optimal dilutions/concentrations should be determined by the end user.
FunctionParticipates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.
Tissue specificityDetected in epithelium from small intestine, with the highest expression at the top of the crypts and a gradient of expression from crypt to villus. Detected in colon epithelium and colon cancer, and in epithelium from mammary gland and carcinomas derived therefrom.
Involvement in diseaseNote=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.
Sequence similaritiesBelongs to the TCF/LEF family. Contains 1 HMG box DNA-binding domain.
Developmental stageHighly expressed in crypt regions and barely detectable in villi in epithelium from fetal small intestine at week 16. At week 22 expression in villi had increased strongly.
DomainThe promoter-specific activation domain interacts with the transcriptional coactivator EP300.
Post-translational modificationsIn vitro, phosphorylated by TNIK. Polysumoylated. Sumoylation is enhanced by PIAS family members and desumoylated by AXAM/SENP2. Sumoylation/desumoylation regulates TCF4 transcription activity in the Wnt signaling pathway without altering interaction with CTNNB1 nor binding DNA.
Cellular localizationNucleus > PML body. Diffuse pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML (promyelocytic leukemia) nuclear bodies.