Disease relevance of MTA3

• Furthermore, the status of the ER pathway modulates the expression of MTA3 as well as epithelial-to-mesenchymal transition in human breast tumors [1].
• MTA3 was exclusively expressed in a subset of cells of ER-positive premalignant lesions but not in carcinomas [2].

High impact information on MTA3

• MTA3 is expressed in the same pattern in germinal centers as BCL-6 [3].
• MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation [3].
• The absence of estrogen receptor or of MTA3 leads to aberrant expression of the transcriptional repressor Snail, a master regulator of epithelial to mesenchymal transitions [4].
• ER signaling upregulates MTA3 levels to negatively modulate Snail-mediated repression of E-cadherin [5].
• MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer [4].

Chemical compound and disease context of MTA3

• Here we have investigated the molecular basis for estrogen and ER-dependent expression of MTA3 in breast cancer cells [6].

Biological context of MTA3

• MTA1, MTA2, and MTA3 are components of the nucleosome remodeling and deacetylation complex, which is associated with adenosine triphosphate-dependent chromatin remodeling and transcriptional regulation [1].
• Molecular dissection of the MTA3 promoter using transient transfection assays identified a composite element required for high-level transcription consisting of an SP1 site in close proximity to a consensus estrogen response element half-site [6].
• Oestrogen receptor alpha represses gene expression by transrepressing the activity of the transcription factors such as nuclear factor-kappaB or by inducing the expression of transcriptional suppressors such as MTA3 [7].
• A recent paper in Cell (Fujita et al., 2003) demonstrates that MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, is an estrogen receptor-regulated inhibitor of the Snail zinc finger transcription factor in breast cancer [8].

Anatomical context of MTA3

• Interestingly, in mammary epithelial cells, MTA3 biosynthesis requires both functional estrogen receptor (ER) and estradiol [6].
• Remarkably, exogenous expression of BCL-6 in a plasma cell line leads, in an MTA3-dependent manner, to repression of plasma cell-specific transcripts, reactivation of the B cell transcriptional program, expression of B lymphocyte cell surface markers, and reprogramming of cell fate [3].

Regulatory relationships of MTA3

• The MTA3 gene thus joins a growing list of loci regulated by both SP1 and ER [6].

Other interactions of MTA3

• We also report the finding of human MTA3, which is highly homologous to both MTA1 and MTA2 [9].
• Depletion of MTA3 by RNAi impairs BCL-6-dependent repression and alters the cell-specific transcriptional pattern characteristic of the B lymphocyte [3].

References