FH and pachyonychia congenita: For example, FH (fumarase), which catalyzes the reversible hydration and dehydration of fumarate, can bind to the c-Jun gene promoter, inhibiting KDM2A activity through local fumarate production and promoting H3K36me2.145 In addition, Oliver et al. demonstrated that 6-aminonicotinamide (6AN), a 6-phosphogluconate dehydrogenase (PGD) inhibitor, induces broad enrichment of H3K9me2 across the CDH2 (N-cadherin) and topoisomerase 2β (TOP2B) genes, causing distant metastasis of PC.146