Figure 5.
Spreading Correlates with Members of the Menin:LEDGF and Super-Elongation Complexes
(A) Example ChIP-seq tracks at SUPT3H in SEM cells.
(B) Heatmap of MLL-AF4, Bio-Cap, Menin, and ENL signal at all 149 spreading MLL-AF4 targets, ordered by length of spreading peak. Scale bar represents tags per bp per 107 reads.
(C) Schematic showing a proposed model for spreading across uCpG regions by MLL-FPs. (i) In the absence of promoter-bound MLL-AF4, CXXC-mediated recruitment of the fusion protein to uCpG-poor regions in the gene body are not stabilized. (ii) Stable CXXC-mediated recruitment to uCpG-rich promoter regions can stabilize nearby MLL-AF4 recruitment at gene body uCpG regions due to common interactions with complex members such as Menin and ENL, whereas distal recruitment events remain unstable. (iii) Because other CXXC proteins, such as KDM2B, do not interact with complex member such as Menin or ENL, promoter-bound KDM2B is not sufficient to stabilize neighboring CXXC-mediated recruitment to CpG-poor uCpG regions in the gene body.
(D) Venn diagram showing the overlap between gene targets of super-enhancers, broad H3K4me3 peaks, and spreading MLL-AF4, in SEM cells.
(E) Heatmap showing ChIP-seq reads of the components indicated at all 149 spreading MLL-AF4 gene targets in SEM cells; scale bar as in (B).
See also Figure S6.