NPM1 mutation reprograms leukemic transcription network via reshaping TAD topology.

C-terminal mutation of Nucleophosmin 1 (NPM1) was thought to be a primary driving event in acute myeloid leukemia (AML) that reprograms leukemic-associated transcription programs to transform hematopoietic stem and progenitor cells (HSPCs). However, molecular mechanisms underlying NPM1-driven leukemogenesis remain elusive. Here, we report that NPM1 activates signature HOX genes and reprograms cell cycle regulators by altering CTCF-driven topologically associated domains (TADs).

A coordinated function of lncRNA HOTTIP and miRNA-196b underpinning leukemogenesis by targeting FAS signaling.

MicroRNAs (miRNAs) may modulate more than 60% of human coding genes and act as negative regulators, whereas long noncoding RNAs (lncRNAs) regulate gene expression on multiple levels by interacting with chromatin, functional proteins, and RNAs such as mRNAs and microRNAs. However, the crosstalk between HOTTIP lncRNA and miRNAs in leukemogenesis remains elusive. Using combined integrated analyses of global miRNA expression profiling and state-of-the-art genomic analyses of chromatin such as ChIRP-seq (HOTTIP binding in genomewide), ChIP-seq, and ATAC-seq, we found that some miRNA genes are directly controlled by HOTTIP.