A KMT2A-AFF1 gene regulatory network highlights the role of core transcription factors and reveals the regulatory logic of key downstream target genes

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Figure 3.
Figure 3.

RUNX1 is a key essential node in the core KMT2A-AFF1 network. (A) Schematic illustrating how CRISPR screen results from Tzelepis et al. (2016) are categorized. Essential genes in HT-29 or HT-1080 were nonspecific essential. Genes not essential in HT-29 or HT-1080 but essential in MOLM-13 or MV4-11 were specific to leukemia. (B) Association of log2 degree centrality (KMT2A-AFF1 GRN) with CRISPR essentiality groups as outlined in A. (C) Degree centrality plotted against stress centrality of KMT2A-AFF1 GRN nodes. (D) Mean absolute stress fold change (FC) response to in silico deletion of GRN nodes and subsequent recalculation of stress centrality. Stress FC is calculated on a per gene basis in the GRN before and after in silico deletion. The top 20 nodes are shown. (E) Stress FC after in silico deletion of RUNX1 or KMT2A-AFF1, plotted against degree. Blue and red indicate positive (FC > 0.1 FC) and negative (FC < −0.1) stress FC, respectively.

This Article

  1. Genome Res. 31: 1159-1173

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