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TCF7L2

Developmental stage

Highly 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.

Domain

The promoter-specific activation domain interacts with the transcriptional coactivator EP300.

Function

Participates 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/TCF4 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.

Involvement in disease

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).

Diabetes mellitus, non-insulin-dependent

NIDDM

A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Post-translational modifications

In vitro, phosphorylated by TNIK.

Phosphorylated at Thr-201 and/or Thr-212 by NLK. Phosphorylation by NLK at these sites inhibits DNA-binding by TCF7L2/TCF4, thereby preventing transcriptional activation of target genes of the canonical Wnt/beta-catenin signaling pathway.

Polysumoylated. Sumoylation is enhanced by PIAS family members and desumoylation is enhanced by SENP2. Sumoylation/desumoylation regulates TCF7L2/TCF4 transcription activity in the Wnt/beta-catenin signaling pathway without altering interaction with CTNNB1 nor binding to DNA.

Sequence similarities

Belongs to the TCF/LEF family.

Tissue specificity

Detected 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.

Cellular localization

  • Nucleus
  • PML body
  • Diffuse pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML (promyelocytic leukemia) nuclear bodies.

Alternative names

  • Transcription factor 7-like 2
  • HMG box transcription factor 4
  • T-cell-specific transcription factor 4
  • T-cell factor 4
  • TCF-4
  • hTCF-4
  • TCF7L2
  • TCF4

Target type

Proteins

Primary research area

Epigenetics

Other research areas

  • Oncology

Molecular weight

67919Da