AMP-activated protein kinase (AMPK) facilitates energetic stress vulnerabilities in acute lymphoblastic leukemia (ALL), but downstream mechanisms are incompletely defined. In their study, Sun and colleagues probed chromatin localization of catalytic subunit AMPKα2 using ChIP-sequencing in control and AMPK activation conditions in an ALL cell line. The authors found that glucose depletion-mediated AMPK activation altered AMPKα2 chromatin binding loci, and that AMPKα2 shared numerous chromatin localization sites with RNA polymerase II (Pol II). Integrated ChIP- and RNA-sequencing analysis identified colocalization of AMPKα2 and Pol II at histone genes and subsequent transcriptional repression of those genes after glucose withdrawal. Bioinformatic analysis presented TATA-Box–Binding Protein–Associated Factor 1 (TAF1) as a putative AMPKα2 binding partner on chromatin, which was verified via coimmunoprecipitation. Mechanistically, the authors found that activated AMPKα2 phosphorylates TAF1, which disrupts TAF1 associations with Pol II and inhibits target gene transcription. The authors confirmed their findings in ALL primary samples and mouse...

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