Unknown

Dataset Information

0

Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.


ABSTRACT: The transcription factor Snail has been described as a direct repressor of E-cadherin expression during development and carcinogenesis; however, the specific mechanisms involved in this process remain largely unknown. Here we show that mammalian Snail requires histone deacetylase (HDAC) activity to repress E-cadherin promoter and that treatment with trichostatin A (TSA) is sufficient to block the repressor effect of Snail. Moreover, overexpression of Snail is correlated with deacetylation of histones H3 and H4 at the E-cadherin promoter, and TSA treatment in Snail-expressing cells reverses the acetylation status of histones. Additionally, we demonstrate that Snail interacts in vivo with the E-cadherin promoter and recruits HDAC activity. Most importantly, we demonstrate an interaction between Snail, histone deacetylase 1 (HDAC1) and HDAC2, and the corepressor mSin3A. This interaction is dependent on the SNAG domain of Snail, indicating that the Snail transcription factor mediates the repression by recruitment of chromatin-modifying activities, forming a multimolecular complex to repress E-cadherin expression. Our results establish a direct causal relationship between Snail-dependent repression of E-cadherin and the modification of chromatin at its promoter.

SUBMITTER: Peinado H 

PROVIDER: S-EPMC303344 | biostudies-other | 2004 Jan

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC1265755 | biostudies-literature
| S-EPMC124246 | biostudies-literature
| S-EPMC2274935 | biostudies-literature
| S-EPMC2628771 | biostudies-literature
| S-EPMC1280278 | biostudies-literature
| S-EPMC2680492 | biostudies-literature
| S-EPMC7791124 | biostudies-literature
| S-EPMC4056552 | biostudies-literature
| S-EPMC5479700 | biostudies-literature
| S-EPMC2475681 | biostudies-literature