Figure 11.2.

Regulation of Ncx1 gene by HDAC’s. Model for the role of acetylation in Ncx1 transcriptional regulation. We speculate that the Ncx1 promoter cycles through at least four kinetic steps. Step 1: Acetylated Nkx2.5 recruits HDAC5, HDAC1, and HDAC2 complex to the promoter. The presence of the HDAC complex allows for low levels of Ncx1 expression. Step 2: When the HDAC complex deacetylates Nkx2.5, HDAC5, HDAC1, and HDAC2 dissociate from the promoter and the HAT, p300, is recruited to the promoter. Step 3: p300 and its associated coactivators stabilize the Poll II complex to allow a high level of transcription of the Ncx1 gene. Step 4: When p300 acetylates Nkx2.5, it dissociates from the promoter and HDAC5, HDAC1, and HDAC2 are recruited to the promoter. Importantly, TSA treatment traps the Ncx1 promoters in the low transcriptional state. HDAC5 is not itself a coactivator, but deacetylation of Nkx2.5 is required for the recruitment of activators to the Ncx1 promoter in response to hypertrophic stimuli