Transcriptional activation by MLL fusion proteins in leukemogenesis Akihiko Yokoyama  Experimental Hematology  Volume 46, Pages 21-30 (February 2017) DOI: 10.1016/j.exphem.2016.10.014 Copyright © 2016 ISEH - International Society for Experimental Hematology Terms and Conditions

Figure 1 Models of gene activation by MLL and MLL fusion complexes. Shown is the expression of self-renewal-related genes in MLL-r leukemia (A) and normal hematopoiesis (B). Diagram has been modified with permission from a previous review article [6]. Experimental Hematology 2017 46, 21-30DOI: (10.1016/j.exphem.2016.10.014) Copyright © 2016 ISEH - International Society for Experimental Hematology Terms and Conditions

Figure 2 Mechanisms of target recognition by MLL and MLL fusion complexes. (A) Schematic structures of MLL and MLL fusion complexes. The domain structures responsible for various protein–protein interactions are indicated. hMBM = high affinity menin binding motif; LBD = LEDGF-binding domain; HBM = HCF-binding motif; AD = activation domain; PS = processing site; Win = WDR5 interaction motif; IBD = integrase-binding domain. Diagram has been modified with permission from a previous review article [6]. (B) Schematic representation of the mechanisms by which MLL and MLL fusion complexes recognize their target chromatin. Experimental Hematology 2017 46, 21-30DOI: (10.1016/j.exphem.2016.10.014) Copyright © 2016 ISEH - International Society for Experimental Hematology Terms and Conditions

Figure 3 Domains/functions required for gene activation by MLL–AEP fusion proteins. (A) Functions of various domains of AF4 depicted schematically. The abilities to transform myeloid progenitors and activate Hoxa9 expression in the form of MTM fusion are indicated, along with various functions. The ALF and pSER domains were originally defined by Nilson et al. [71]. Their definition was slightly modified because the DLXLS motif, which was originally included in the ALF domain, was included in the pSER domain in our reports [82,92]. (B) Functions of various subdomains in the pSER domain depicted schematically. Experimental Hematology 2017 46, 21-30DOI: (10.1016/j.exphem.2016.10.014) Copyright © 2016 ISEH - International Society for Experimental Hematology Terms and Conditions

Figure 4 Model of gene activation by MLL–AEP fusion proteins. The rate-limiting step carried out by MLL–AEP fusion proteins is highlighted in red. Experimental Hematology 2017 46, 21-30DOI: (10.1016/j.exphem.2016.10.014) Copyright © 2016 ISEH - International Society for Experimental Hematology Terms and Conditions

Experimental Hematology 2017 46, 21-30DOI: (10. 1016/j. exphem. 2016 Copyright © 2016 ISEH - International Society for Experimental Hematology Terms and Conditions