Figure 2.
Somatic mutations in CREs prefer to accumulate on chromatin regions bound by master transcription factors essential for APL. (A) Master transcription factors identified by the CRC modeling using H3K27ac ChIP-seq data of 16 APL samples. (B) Enrichment of binding regions for master transcription factors within mutated CREs. The enrichment level of binding regions for the indicated transcription factor in mutated CREs was analyzed by the Fisher’s exact test. (C) Enrichment analysis of DNA recognition motifs for the identified master transcription factors within mutated CREs compared with nonmutated CREs. The position weight matrices of master transcription factors and their paralogs for motif enrichment analysis were downloaded from JASPAR (http://jaspar.genereg.net). The top 3 enriched motifs (JASPAR ID) for the indicated transcription factor family were listed (eg, MA0100.3, MA0776.1, and MA0777.1 for MYB, MYBL1, and MYBL2, respectively). Box plot represents the median, interquartile range, and minimum and maximum quartile from motif enrichment analysis of 200 random subsampling from background regions. (D) Mutation enrichment analysis for master transcription factors over binding regions centered on DNA recognition motifs and the surrounding area. Z scores are computed based on a permutation test, and the dashed line indicates a P value < .05 significance threshold. mutCRE, mutated CRE.