Figure 1 | Oncogene

Figure 1

From: Epigenetic therapies by targeting aberrant histone methylome in AML: molecular mechanisms, current preclinical and clinical development

Figure 1

Roles of HMTs and KDMs in MLL-driven transcription. (a) MLL fusion complexes are assembled by recruiting a body of important components (super elongation complex, polymerase-associated factor complex, MENIN and LEDGF) to target and facilitate expression of crucial leukaemogenic genes, such as HOXs, MEIS and MEF2C, where HMTs (DOT1L, PRMT1 and MLL) are involved to add active methyl marks (H3K79me2/3, H4R3me2a and H3K4me3), respectively. BRD4, a histone mark reader, is essential for the recruitment of MLL fusions. (b) In addition to enrichment of active marks, KDMs (e.g., KDM4C, JMJD1C) on the other hand remove repressive marks (H3K9me3) to underpin the active status. Although LSD1 has been suggested to remove H3K4me1/2 marks in MLL leukaemia, its relevance to leukaemia suppression is still largely unknown. (c) KDM5B negatively regulates MLL target genes through demethylation of H3K4me3 active mark. Black arrows indicate methylation, whereas bent red arrows represent demethylation.

Back to article page