Molecular analysis of a candidate metastasis-associated gene, MTA1: Possible interaction with histone deacetylase 1

We previously identified a novel rat candidate metastasis-associated gene, mta1, based on its differential expression in highly metastatic cells compa red to nonmetastatic cells. Furthermore, we showed that overexpression of i ts human counterpart, MTA1, correlated with the invasiveness or lymph node metastasis of gastric, colorectal and esophageal carcinomas. The aim of thi s study was to analyze the domains of the MTA1 and investigate the function (s) of this protein. Structural analysis revealed that the MTA1 protein con tained a GATA-like zinc-finger domain, a leucine zipper domain, a SANT doma in similar to the DNA binding domain of myb-related proteins, a src homolog y 3-binding domain important in protein-protein interactions, two highly ac idic regions characteristic of the acidic activation domains of many transc ription factors, and nuclear localization signals. Immunofluorescence stain ing of COS-7 cells transfected with a myc-epitope-tagged MTA1 expression ve ctor clearly showed nuclear localization of MTA1. Coimmunoprecipitation of myc-tagged MTA1 and FLAG-tagged histone deacetylase 1 (HDAC1), followed by western blot analysis using anti-myc and anti-FLAG monoclonal antibodies sh owed that MTA1 physically bound with HDAC1 in COS-7 cells. Together with th e recent finding that the NURD (nucleosome remodeling and histone deacetyla se activities) complex contains an MTA1-related gene product, named MTA2, M TA1 may be another component of this complex and be involved in the alterat ion of chromatin structure and transcription repression.