For instance, the expression of ACVRL1/ALK1, which is dominantly expressed in endothelial cells, is controlled by CpG island methylation, mediated by transcription factor Sp1 on the ACVRL1/ALK1 promoter region, suggesting possible involvement of the epigenetic mechanism of ACVRL1/ALK1 in PAH.58 In recent times, miR-656 was reported to directly target BMPR1A/ALK3 in glioma cell lines.59 In the case of BMPR1B/ALK6, it was suggested that the expression of this gene can be tightly regulated through the DNA methylation status of the species-conserved 5′-CpG island in the promoter region. This evidence concerns the gene BMPR1A and pulmonary arterial hypertension.