Of the transcription factors known or predicted to regulate HCN4 (AP1, Isl1, Mef2c, Nkx2.5, NRSF, Tbx3 and Tbx18), two (Nkx2.5 and Tbx3) did not change in the sinus node in heart failure (Supplementary Fig. 4). The gene discussed is ISL1; the disease is heart failure.