Defining heterogeneity in core regulatory circuitry reveals HOXB3 condensation as a potential target in glioblastoma

Miller, K. D. et al. Brain and other central nervous system tumor statistics, 2021. CA Cancer J. Clin. 71, 381–406 (2021).

PubMed  Google Scholar 

Aldape, K. et al. Challenges to curing primary brain tumours. Nat. Rev. Clin. Oncol. 16, 509–520 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Prager, B. C., Xie, Q., Bao, S. & Rich, J. N. Cancer stem cells: the architects of the tumor ecosystem. Cell Stem Cell 24, 41–53 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hambardzumyan, D. & Bergers, G. Glioblastoma: defining tumor niches. Trends Cancer 1, 252–265 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Terekhanova, N. V. et al. Epigenetic regulation during cancer transitions across 11 tumour types. Nature 623, 432–441 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Karimi, E. et al. Single-cell spatial immune landscapes of primary and metastatic brain tumours. Nature 614, 555–563 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hnisz, D. et al. Super-enhancers in the control of cell identity and disease. Cell 155, 934–947 (2013).

Article  CAS  PubMed  Google Scholar 

Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947–956 (2005).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nguyen, T. T. T. et al. HDAC inhibitors elicit metabolic reprogramming by targeting super-enhancers in glioblastoma models. J. Clin. Invest. 130, 3699–3716 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu, B. et al. Pharmacological inhibition of core regulatory circuitry liquid-liquid phase separation suppresses metastasis and chemoresistance in osteosarcoma. Adv. Sci. 8, e2101895 (2021).

Article  Google Scholar 

Blayney, J. W. et al. Super-enhancers include classical enhancers and facilitators to fully activate gene expression. Cell 186, 5826–5839.e5818 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dębek, S. & Juszczyński, P. Super enhancers as master gene regulators in the pathogenesis of hematologic malignancies. Biochim. Biophys. Acta Rev. Cancer 1877, 188697 (2022).

Article  PubMed  Google Scholar 

Wu, S. J. et al. Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression. Nat. Biotechnol. 39, 819–824 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bartosovic, M., Kabbe, M. & Castelo-Branco, G. Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues. Nat. Biotechnol. 39, 825–835 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi, B. et al. UTX condensation underlies its tumour-suppressive activity. Nature 597, 726–731 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee, K. H. et al. C9orf72 dipeptide repeats impair the assembly, dynamics, and function of membrane-less organelles. Cell 167, 774–788.e717 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

White, M. R. et al. C9orf72 poly(PR) dipeptide repeats disturb biomolecular phase separation and disrupt nucleolar function. Mol. Cell 74, 713–728.e716 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morgan, R. et al. Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma. Cancer Res. 67, 5806–5813 (2007).

Article  CAS  PubMed  Google Scholar 

Shah, N. & Sukumar, S. The Hox genes and their roles in oncogenesis. Nat. Rev. Cancer 10, 361–371 (2010).

Article  CAS  PubMed  Google Scholar 

Wilmerding, A. et al. HoxB genes regulate neuronal delamination in the trunk neural tube by controlling the expression of Lzts1. Development 148, dev195404 (2021).

Article  CAS  PubMed  Google Scholar 

Afzal, Z. et al. Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube. Development 150, dev201259 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Okuda, T., Nishimura, M., Nakao, M. & Fujita, Y. RUNX1/AML1: a central player in hematopoiesis. Int J. Hematol. 74, 252–257 (2001).

Article  CAS  PubMed  Google Scholar 

Carro, M. S. et al. The transcriptional network for mesenchymal transformation of brain tumours. Nature 463, 318–325 (2010).

Article  CAS  PubMed  Google Scholar 

Lovén, J. et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153, 320–334 (2013).

Article  PubMed  PubMed Central  Google Scholar 

Kwiatkowski, N. et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature 511, 616–620 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eid, A., Alshareef, S. & Mahfouz, M. M. CRISPR base editors: genome editing without double-stranded breaks. Biochem. J. 475, 1955–1964 (2018).

Article  CAS  PubMed  Google Scholar 

Mill, C. P. et al. RUNX1-targeted therapy for AML expressing somatic or germline mutation in RUNX1. Blood 134, 59–73 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Feng, J., Liu, T., Qin, B., Zhang, Y. & Liu, X. S. Identifying ChIP-seq enrichment using MACS. Nat. Protoc. 7, 1728–1740 (2012).

Article  CAS  PubMed  Google Scholar 

Zheng, W. et al. High-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome. Science 376, eabm1483 (2022).

Article  CAS  PubMed  Google Scholar 

Granja, J. M. et al. ArchR is a scalable software package for integrative single-cell chromatin accessibility analysis. Nat. Genet. 53, 403–411 (2021).

Article  CAS  PubMed  PubMed Central 

Comments (0)

No login
gif