Fig. 6. Transcriptional regulation by Smads. Two examples, one for gene induction and one for gene repression are shown. Chromatin in nucleosomal configuration is depicted by an arrow indicating promoter activation and a vertical line depicting promoter silencing. Smads are shown as heterodimers of phosphorylated (small black circle) R-Smad–Smad4 according to Fig. 2. Smads interact with DNA-binding transcription factors (TF) and recruit co-activators (p300) or co-repressors that sequentially associate with HDACs. The former results in transcription factor and histone acetylation (Ac), whereas the latter leads to deacetylation. These models take into account only the role of protein acetylation in transcriptional regulation. For references, see Massagué and Wotton (Massagué and Wotton, 2000).