Tcf1 and Lef1 pack their own HDAC

Abstract

The transcription factors Tcf1 and Lef1 have intrinsic histone-deacetylase activity that is required for the repression of CD4⁺ T cell-lineage genes in CD8⁺ T cells.

Figure 1

Tcf1 and Lef1 regulate gene expression in CD8⁺ thymocytes through intrinsic HDAC activity. The transcription factors Tcf1 and Lef1 contain an HDAC domain that reverses the acetylation of histones and is required for the repression of multiple genes in CD8⁺ T cells (top). in Tcf7^−/−Lef1^−/− mice, there is derepression of genes associated with the CD4⁺ lineage and genes encoding effector molecules associated with cytotoxic T cells, in CD8⁺ thymocytes. Complementation of Tcf1- and Lef1-deficient thymocytes with HDAC-deficient Tcf1 fails to fully ‘rescue’ the aberrant gene expression of CD8⁺ thymocytes (middle). There is less dependence on the HDAC domain of Tcf1 for the differentiation of CD4⁺ thymocytes, which raises the possibility of context-dependent requirements for the HDAC domain at lineage-regulating genomic loci. Thus, gene activation at some loci might involve cofactors that inhibit HDAC function (bottom). CBP, histone acetyltransferase.