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Bivalent genes are regulated by a balance between repressive Polycomb group proteins and activating trithorax group proteins. A new study has revealed that MENIN, an accessory component of KMT2A/B methyltransferase complexes, has an unorthodox role in repressing bivalent genes, alongside Polycomb repressive complexes.
Using somatic genome editing and Tuba-seq, Tang et al. uncover a previously uncharacterized role for HRAS and NRAS in impairing KRAS–KRAS interaction to suppress lung tumour growth.
With whole-genome screens using a bivalent MHC class I gene expression readout, Sparbier et al. identify opposing roles for Menin and KMT2A/B in modulating activating H3K4me3 versus repressive H3K27me3 at bivalent promoters to regulate gene activation.
Polycomb repressive complexes 1 and 2 both regulate maintenance of X inactivation in extra-embryonic lineages of post-implantation embryos by affecting overlapping yet different genes, thus implying potentially independent roles for the two complexes.
Stewart-Morgan et al. present isolation of DNA by 5-ethynyl-deoxyuridine labelling for mass spectrometry, a highly sensitive, quantitative mass spectrometry-based method for measuring DNA modifications on metabolically labelled DNA. They apply it to study DNA methylation and hydroxymethylation propagation.
PD-1 and PD-L1 are important immune checkpoint molecules that modulate T cell activity. A study now shows that PD-1 marks leukaemia stem cells (LSCs) in T cell acute lymphoblastic leukaemia and reveals therapeutic opportunities to target LSCs via anti-PD-1 therapy.
Jung-Garcia et al. dissect the contributions of isoforms of the inner nuclear membrane protein LAP1 to nuclear envelope blebbing, constrained migration and invasion in melanoma cells.
Xu, Zhang, Xuan et al. show that PD-1 signalling defines a population of leukaemia stem cells with features of quiescence, drug resistance and protection against cell death, ablation of which suppresses disease progression of mouse and human T-ALL.
Yelagandula et al. show that ZFP462 interacts with G9A/GLP to modulate enhancers with binding sites for embryonic stem cell-specific transcription factors, thereby regulating lineage specification during neural differentiation of mouse embryonic stem cells.
Cui et al. identify an important role for MLL3 in regulating the hybrid epithelial–mesenchymal transition state in breast cancer and show that deletion of MLL3 enhances metastatic capacity through increased IFNγ signalling.
Lee et al. uncover a previously uncharacterized role of OASL in virus-induced necroptosis. OASL chaperones the assembly of RIPK3 and ZBP1 via liquid-liquid phase separation, which induces RIPK3 and necroptosis activation, thereby modulating inflammation and host defence against viral infection.