PLX040193

GSE142198: Chromatin Topology Reorganization and Transcription Repression by PML/RAR in Acute Promyeloid Leukemia (RNA-seq)

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Acute promyeloid leukemia (APL) is characterized by the oncogenic fusion protein PML/RAR, a major etiological agent in APL. Although PML/RAR is critical, the molecular mechanisms remains largely unknown. Here, using an inducible system, we comprehensively analyzed the 3D genome organization in myloid cells and its reorganizationn after PML/RAR induction, and performed additional analysis in patient-derived APL cells with native PML/RAR. We discovered that PML/RAR mediate extensive chromatin interactions genome-wide. Globally, it redefine the chromatin topology of the in myloid genome toward a more condensed configuration in APL cells; locally, it intrude RNAPII-associated interaction dmains, interrupt myeloid-specific transcription factors binding at enhancers and super-enahncers, and lead to transcriptional repression of genes critical for myeloid differentiation and maturation. Together, our results provide novel insights of a topological framework for PML/RARs roles in transforming myeloid into leukemia, likely a general mechanism for oncogenic fusion proteins in cancers. SOURCE: Yijun Ruan (yijun.ruan@jax.org) - Ruan The Jackson Laboratory