دورية أكاديمية
أعرض في EDS

Collateral lethality between HDAC1 and HDAC2 exploits cancer-specific NuRD complex vulnerabilities.

التفاصيل البيبلوغرافية
العنوان: Collateral lethality between HDAC1 and HDAC2 exploits cancer-specific NuRD complex vulnerabilities.
المؤلفون: Zhang Y; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Remillard D; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Onubogu U; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA., Karakyriakou B; Massachusetts General Hospital Cancer Center, Charlestown, MA, USA., Asiaban JN; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Ramos AR; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Bowland K; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Bishop TR; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Barta PA; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Nance S; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA., Durbin AD; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA., Ott CJ; Massachusetts General Hospital Cancer Center, Charlestown, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT & Harvard, Cambridge, MA, USA., Janiszewska M; Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA., Cravatt BF; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA., Erb MA; Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA. michaelerb@scripps.edu.
المصدر: Nature structural & molecular biology [Nat Struct Mol Biol] 2023 Aug; Vol. 30 (8), pp. 1160-1171. Date of Electronic Publication: 2023 Jul 24.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101186374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1545-9985 (Electronic) Linking ISSN: 15459985 NLM ISO Abbreviation: Nat Struct Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York : Nature Pub. Group, c2004-
مواضيع طبية MeSH: Multiple Myeloma*/genetics , Neuroblastoma*/genetics, Humans ; Mi-2 Nucleosome Remodeling and Deacetylase Complex/genetics ; Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism ; Histone Deacetylase 1/genetics ; Histone Deacetylase 1/metabolism ; Gene Expression Regulation ; Nucleosomes ; Histone Deacetylase 2/genetics ; Histone Deacetylase 2/metabolism
مستخلص: Transcriptional co-regulators have been widely pursued as targets for disrupting oncogenic gene regulatory programs. However, many proteins in this target class are universally essential for cell survival, which limits their therapeutic window. Here we unveil a genetic interaction between histone deacetylase 1 (HDAC1) and HDAC2, wherein each paralog is synthetically lethal with hemizygous deletion of the other. This collateral synthetic lethality is caused by recurrent chromosomal deletions that occur in diverse solid and hematological malignancies, including neuroblastoma and multiple myeloma. Using genetic disruption or dTAG-mediated degradation, we show that targeting HDAC2 suppresses the growth of HDAC1-deficient neuroblastoma in vitro and in vivo. Mechanistically, we find that targeted degradation of HDAC2 in these cells prompts the degradation of several members of the nucleosome remodeling and deacetylase (NuRD) complex, leading to diminished chromatin accessibility at HDAC2-NuRD-bound sites of the genome and impaired control of enhancer-associated transcription. Furthermore, we reveal that several of the degraded NuRD complex subunits are dependencies in neuroblastoma and multiple myeloma, providing motivation to develop paralog-selective HDAC1 or HDAC2 degraders that could leverage HDAC1/2 synthetic lethality to target NuRD vulnerabilities. Altogether, we identify HDAC1/2 collateral synthetic lethality as a potential therapeutic target and reveal an unexplored mechanism for targeting NuRD-associated cancer dependencies.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
References: Shortt, J., Ott, C. J., Johnstone, R. W. & Bradner, J. E. A chemical probe toolbox for dissecting the cancer epigenome. Nat. Rev. Cancer 17, 160–183 (2017). (PMID: 2822864310.1038/nrc.2016.148)
Chang, L., Ruiz, P., Ito, T. & Sellers, W. R. Targeting pan-essential genes in cancer: challenges and opportunities. Cancer Cell. 39, 466–479 (2021). (PMID: 33450197815767110.1016/j.ccell.2020.12.008)
Seto, E. & Yoshida, M. Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb. Perspect. Biol. 6, a018713–a018713 (2014). (PMID: 24691964397042010.1101/cshperspect.a018713)
Bachy, E. et al. Final analysis of the Ro-CHOP Phase III Study (Conducted by LYSA): romidepsin plus CHOP in patients with peripheral T-cell lymphoma. Blood 136, 32–33 (2020). (PMID: 10.1182/blood-2020-134440)
Falkenberg, K. J. & Johnstone, R. W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat. Rev. Drug Discov. 13, 673–691 (2014). (PMID: 2513183010.1038/nrd4360)
Kelly, R. D. W. & Cowley, S. M. The physiological roles of histone deacetylase (HDAC) 1 and 2: complex co-stars with multiple leading parts. Biochem. Soc. Trans. 41, 741–749 (2013). (PMID: 2369793310.1042/BST20130010)
Millard, C. J., Watson, P. J., Fairall, L., Schwabe, J. W. R. & Targeting Class, I. Histone deacetylases in a ‘complex’ environment. Trends Pharmacol. Sci. 38, 363–377 (2017). (PMID: 2813925810.1016/j.tips.2016.12.006)
Taunton, J., Hassig, C. A. & Schreiber, S. L. A mammalian histone deacetylase related to the yeast transciptional regulator Rpd3p. Science 272, 408–411 (1996). (PMID: 860252910.1126/science.272.5260.408)
Li, Y. & Seto, E. HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harb. Perspect. Med. 6, a026831 (2016). (PMID: 27599530504668810.1101/cshperspect.a026831)
Dovey, O. M., Foster, C. T. & Cowley, S. M. Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc. Natl Acad. Sci. USA 107, 8242–8247 (2010). (PMID: 20404188288951310.1073/pnas.1000478107)
Lagger, G. et al. Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J. 21, 2672–2681 (2002). (PMID: 1203208012604010.1093/emboj/21.11.2672)
Jamaladdin, S. et al. Histone deacetylase (HDAC) 1 and 2 are essential for accurate cell division and the pluripotency of embryonic stem cells. Proc. Natl Acad. Sci. USA 111, 9840–9845 (2014). (PMID: 24958871410337910.1073/pnas.1321330111)
Yamaguchi, T. et al. Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progression. Genes Dev. 24, 455–469 (2010). (PMID: 20194438282784110.1101/gad.552310)
Wilting, R. H. et al. Overlapping functions of Hdac1 and Hdac2 in cell cycle regulation and haematopoiesis. EMBO J. 29, 2586–2597 (2010). (PMID: 20571512292869010.1038/emboj.2010.136)
LeBoeuf, M. et al. Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Dev. Cell 19, 807–818 (2010). (PMID: 21093383300333810.1016/j.devcel.2010.10.015)
Heideman, M. R. et al. Dosage-dependent tumor suppression by histone deacetylases 1 and 2 through regulation of c-Myc collaborating genes and p53 function. Blood 121, 2038–2050 (2013). (PMID: 23327920359696310.1182/blood-2012-08-450916)
Dovey, O. M. et al. Histone deacetylase 1 and 2 are essential for normal T-cell development and genomic stability in mice. Blood 121, 1335–1344 (2013). (PMID: 2328786810.1182/blood-2012-07-441949)
Matthews, G. M. et al. Functional–genetic dissection of HDAC dependencies in mouse lymphoid and myeloid malignancies. Blood 126, 2392–2403 (2015). (PMID: 26447190465376710.1182/blood-2015-03-632984)
Stubbs, M. C. et al. Selective inhibition of HDAC1 and HDAC2 as a potential therapeutic option for B-ALL. Clin. Cancer Res. 21, 2348–2358 (2015). (PMID: 25688158443381110.1158/1078-0432.CCR-14-1290)
Frumm, S. M. et al. Selective HDAC1/HDAC2 inhibitors induce neuroblastoma differentiation. Chem. Biol. 20, 713–725 (2013). (PMID: 23706636391944910.1016/j.chembiol.2013.03.020)
Ito, T. et al. Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers. Nat. Genet. 53, 1664–1672 (2021). (PMID: 3485795210.1038/s41588-021-00967-z)
DeWeirdt, P. C. et al. Optimization of AsCas12a for combinatorial genetic screens in human cells. Nat. Biotechnol. 39, 94–104 (2021). (PMID: 3266143810.1038/s41587-020-0600-6)
Huang, A., Garraway, L. A., Ashworth, A. & Weber, B. Synthetic lethality as an engine for cancer drug target discovery. Nat. Rev. Drug Discov. 19, 23–38 (2020). (PMID: 3171268310.1038/s41573-019-0046-z)
Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917 (2005). (PMID: 1582996610.1038/nature03443)
Hoffman, G. R. et al. Functional epigenetics approach identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers. Proc. Natl Acad. Sci. USA 111, 3128–3133 (2014). (PMID: 24520176393988510.1073/pnas.1316793111)
Wilson, B. G. et al. Residual complexes containing SMARCA2 (BRM) underlie the oncogenic drive of SMARCA4 (BRG1) mutation. Mol. Cell. Biol. 34, 1136–1144 (2014). (PMID: 24421395395803410.1128/MCB.01372-13)
Oike, T. et al. A synthetic lethality-based strategy to treat cancers harboring a genetic deficiency in the chromatin remodeling factor BRG1. Cancer Res. 73, 5508–5518 (2013). (PMID: 2387258410.1158/0008-5472.CAN-12-4593)
Ogiwara, H. et al. Targeting p300 addiction in CBP-deficient cancers causes synthetic lethality by apoptotic cell death due to abrogation of MYC expression. Cancer Discov. 6, 430–445 (2016). (PMID: 2660352510.1158/2159-8290.CD-15-0754)
Lelij, P. et al. Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse cancer contexts. eLife 6, e26980 (2017). (PMID: 28691904553183010.7554/eLife.26980)
Parrish, P. C. R. et al. Discovery of synthetic lethal and tumor suppressor paralog pairs in the human genome. Cell Rep. 36, 109597 (2021). (PMID: 34469736853430010.1016/j.celrep.2021.109597)
Malone, C. F. et al. Selective modulation of a pan-essential protein as a therapeutic strategy in cancer. Cancer Discov. 11, 2282–2299 (2021). (PMID: 33883167841901210.1158/2159-8290.CD-20-1213)
Tsherniak, A. et al. Defining a cancer dependency map. Cell 170, 564–576 (2017). (PMID: 28753430566767810.1016/j.cell.2017.06.010)
Meyers, R. M. et al. Computational correction of copy number effect improves specificity of CRISPR–Cas9 essentiality screens in cancer cells. Nat. Genet. 49, 1779–1784 (2017). (PMID: 29083409570919310.1038/ng.3984)
Caron, H. et al. Allelic loss of chromosome 1p36 in neuroblastoma is of preferential maternal origin and correlates with N–myc amplification. Nat. Genet. 4, 187–190 (1993). (PMID: 810229810.1038/ng0693-187)
Maris, J. M. et al. Significance of chromosome 1p loss of heterozygosity in neuroblastoma. Cancer Res. 55, 4664–4669 (1995). (PMID: 7553646)
Janoueix-Lerosey, I. et al. Gene expression profiling of 1p35-36 genes in neuroblastoma. Oncogene 23, 5912–5922 (2004). (PMID: 1519513810.1038/sj.onc.1207784)
Komotar, R. J., Otten, M. L., Starke, R. M. & Anderson, R. C. E. Chromosome 1p and 11q deletions and outcome in neuroblastoma—a critical review. Clin. Med Oncol. 2, 419–420 (2008). (PMID: 218923093161664)
Merup, M. et al. 6q deletions in acute lymphoblastic leukemia and non-Hodgkin’s lymphomas. Blood 91, 3397–3400 (1998). (PMID: 955839810.1182/blood.V91.9.3397)
Thelander, E. F. et al. Characterization of 6q deletions in mature B cell lymphomas and childhood acute lymphoblastic leukemia. Leuk. Lymphoma 49, 477–487 (2008). (PMID: 1829752410.1080/10428190701817282)
Taborelli, M. et al. Chromosome band 6q deletion pattern in malignant lymphomas. Cancer Genet Cytogenet 165, 106–113 (2006). (PMID: 1652760410.1016/j.cancergencyto.2005.06.025)
Aktas Samur, A. et al. Deciphering the chronology of copy number alterations in multiple myeloma. Blood Cancer J. 9, 39 (2019).
Durbin, A. D. et al. Selective gene dependencies in MYCN-amplified neuroblastoma include the core transcriptional regulatory circuitry. Nat. Genet. 50, 1240–1246 (2018). (PMID: 30127528638647010.1038/s41588-018-0191-z)
Zeid, R. et al. Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma. Nat. Genet. 50, 515–523 (2018). (PMID: 29379199631039710.1038/s41588-018-0044-9)
Dharia, N. V. et al. A first-generation pediatric cancer dependency map. Nat. Genet. 53, 529–538 (2021). (PMID: 33753930804951710.1038/s41588-021-00819-w)
Chen, L. et al. CRISPR–Cas9 screen reveals a MYCN-amplified neuroblastoma dependency on EZH2. J. Clin. Invest. 128, 446–462 (2018). (PMID: 2920247710.1172/JCI90793)
Ghandi, M. et al. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature 569, 503–508 (2019). (PMID: 31068700669710310.1038/s41586-019-1186-3)
García-López, J. et al. Large 1p36 deletions affecting Arid1a locus facilitate mycn-driven oncogenesis in neuroblastoma. Cell Rep. 30, 454–464 (2020). (PMID: 31940489902221710.1016/j.celrep.2019.12.048)
Shi H., et al. ARID1A loss in neuroblastoma promotes the adrenergic-to-mesenchymal transition by regulating enhancer-mediated gene expression. Sci Adv. 6, eaaz3440 (2020).
Cerami, E. et al. The cBio Cancer Genomics Portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401–404 (2012). (PMID: 2258887710.1158/2159-8290.CD-12-0095)
Erb, M. A. et al. Transcription control by the ENL YEATS domain in acute leukaemia. Nature 543, 270–274 (2017). (PMID: 28241139549722010.1038/nature21688)
Nabet, B. et al. The dTAG system for immediate and target-specific protein degradation. Nat. Chem. Biol. 14, 431–441 (2018). (PMID: 29581585629591310.1038/s41589-018-0021-8)
Jaeger, M. G. & Winter, G. E. Fast-acting chemical tools to delineate causality in transcriptional control. Mol. Cell 81, 1617–1630 (2021). (PMID: 3368974910.1016/j.molcel.2021.02.015)
Zhang, Y. & Erb, M. A. Enabling cancer target validation with genetically encoded systems for ligand-induced protein degradation. Curr. Res Chem. Biol. 1, 100011 (2021). (PMID: 10.1016/j.crchbi.2021.100011)
Skene, P. J., Henikoff, J. G. & Henikoff, S. Targeted in situ genome-wide profiling with high efficiency for low cell numbers. Nat. Protoc. 13, 1006–1019 (2018). (PMID: 2965105310.1038/nprot.2018.015)
Herzog, V. A. et al. Thiol-linked alkylation of RNA to assess expression dynamics. Nat. Methods 14, 1198–1204 (2017). (PMID: 28945705571221810.1038/nmeth.4435)
Shearstone, J. R. et al. Chemical inhibition of histone deacetylases 1 and 2 induces fetal hemoglobin through activation of GATA2. PLoS ONE 11, 1–27 (2016). (PMID: 10.1371/journal.pone.0153767)
Whyte, W. A. et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153, 307–319 (2013). (PMID: 23582322365312910.1016/j.cell.2013.03.035)
Schölz, C. et al. Acetylation site specificities of lysine deacetylase inhibitors in human cells. Nat. Biotechnol. 33, 415–425 (2015). (PMID: 2575105810.1038/nbt.3130)
Marques, J. G. et al. NURD subunit CHD4 regulates super-enhancer accessibility in rhabdomyosarcoma and represents a general tumor dependency. eLife 9, 1–30 (2020). (PMID: 10.7554/eLife.54993)
Gryder, B. E. et al. Histone hyperacetylation disrupts core gene regulatory architecture in rhabdomyosarcoma. Nat. Genet. 51, 1714–1722 (2019). (PMID: 31784732688657810.1038/s41588-019-0534-4)
Emdal, K. B. et al. Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma. Sci. Signal 11, eaap9752 (2018). (PMID: 3045928310.1126/scisignal.aap9752)
Rihani, A., Vandesompele, J., Speleman, F. & Van Maerken, T. Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma. Cancer Cell Int. 15, 76 (2015). (PMID: 26225123451853210.1186/s12935-015-0224-y)
Xiong, Y. et al. Chemo-proteomics exploration of HDAC degradability by small molecule degraders. Cell Chem. Biol. 28, 1514–1527 (2021). (PMID: 3431473010.1016/j.chembiol.2021.07.002)
Hsu, J. H. R. et al. EED-Targeted PROTACs Degrade EED, EZH2, and SUZ12 in the PRC2 Complex. Cell Chem. Biol. 27, 41–46 (2020). (PMID: 3178618410.1016/j.chembiol.2019.11.004)
Farnaby, W. et al. BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design. Nat. Chem. Biol. 15, 672–680 (2019). (PMID: 31178587660087110.1038/s41589-019-0294-6)
Schick, S. et al. Acute BAF perturbation causes immediate changes in chromatin accessibility. Nat. Genet. 53, 269–278 (2021). (PMID: 33558760761408210.1038/s41588-021-00777-3)
Sher, F. et al. Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis. Nat. Genet. 51, 1149–1159 (2019). (PMID: 31253978665027510.1038/s41588-019-0453-4)
Vinogradova, E. V. et al. An activity-guided map of electrophile-cysteine interactions in primary human T cells. Cell 182, 1009–1026 (2020). (PMID: 32730809777562210.1016/j.cell.2020.07.001)
Denslow, S. A. & Wade, P. A. The human Mi-2/NuRD complex and gene regulation. Oncogene 26, 5433–5438 (2007). (PMID: 1769408410.1038/sj.onc.1210611)
Low, J. K. K. et al. The nucleosome remodeling and deacetylase complex has an asymmetric, dynamic, and modular architecture. Cell Rep. 33, 108450 (2020). (PMID: 33264611890838610.1016/j.celrep.2020.108450)
Millard, C. J. et al. The structure of the core NuRD repression complex provides insights into its interaction with chromatin. eLife 5, 1–21 (2016). (PMID: 10.7554/eLife.13941)
Reid, X. J., Low, J. K. K. & Mackay, J. P. A NuRD for all seasons. Trends Biochem. Sci. 48, 11–25 (2023). (PMID: 3579861510.1016/j.tibs.2022.06.002)
Buenrostro, J. D., Wu, B., Chang, H. Y. & Greenleaf, W. J. ATAC-seq: a method for assaying chromatin accessibility genome-wide. Curr. Protoc. Mol. Biol. 2015, 21.29.1–21.29.9 (2015).
Gryder, B. E. et al. Chemical genomics reveals histone deacetylases are required for core regulatory transcription. Nat. Commun. 10, 3004 (2019). (PMID: 31285436661436910.1038/s41467-019-11046-7)
Qu, K. et al. Chromatin accessibility landscape of cutaneous T cell lymphoma and dynamic response to HDAC inhibitors. Cancer Cell 32, 27–41 (2017). (PMID: 28625481555938410.1016/j.ccell.2017.05.008)
Pan, J. et al. Interrogation of mammalian protein complex structure, function, and membership using genome-scale fitness screens. Cell Syst. 6, 555–568 (2018). (PMID: 29778836615290810.1016/j.cels.2018.04.011)
Michel, B. C. et al. A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nat. Cell Biol. 20, 1410–1420 (2018). (PMID: 30397315669838610.1038/s41556-018-0221-1)
Lai, A. Y. & Wade, P. A. Cancer biology and NuRD: a multifaceted chromatin remodelling complex. Nat. Rev. Cancer 11, 588–596 (2011). (PMID: 21734722415752410.1038/nrc3091)
Bornelöv, S. et al. The nucleosome remodeling and deacetylation complex modulates chromatin structure at sites of active transcription to fine-tune gene expression. Mol. Cell 71, 56–72 (2018). (PMID: 30008319603972110.1016/j.molcel.2018.06.003)
Smalley, J. P. et al. Optimization of class I histone deacetylase PROTACs reveals that HDAC1/2 degradation is critical to induce apoptosis and cell arrest in cancer cells. J. Med. Chem. 65, 5642–5659 (2022). (PMID: 35293758901441210.1021/acs.jmedchem.1c02179)
Smalley, J. P. et al. PROTAC-mediated degradation of class i histone deacetylase enzymes in corepressor complexes. Chem. Commun. 56, 4476–4479 (2020). (PMID: 10.1039/D0CC01485K)
Cross, J. M. et al. A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras. RSC Med Chem. 13, 1634–1639 (2022). (PMID: 36545434974992410.1039/D2MD00199C)
Baker, I. M., Smalley, J. P., Sabat, K. A., Hodgkinson, J. T. & Cowley, S. M. Comprehensive transcriptomic analysis of novel class I HDAC proteolysis targeting chimeras (PROTACs). Biochemistry 62, 645–656 (2022). (PMID: 3594804710.1021/acs.biochem.2c00288)
Scholes, N. S., Mayor-Ruiz, C. & Winter, G. E. Identification and selectivity profiling of small-molecule degraders via multi-omics approaches. Cell Chem. Biol. 28, 1048–1060 (2021). (PMID: 3381181210.1016/j.chembiol.2021.03.007)
Remillard, D. et al. Degradation of the BAF complex factor BRD9 by heterobifunctional ligands. Angew. Chem. Int. Ed. 56, 5738–5743 (2017). (PMID: 10.1002/anie.201611281)
Olson, C. M. et al. Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation. Nat. Chem. Biol. 14, 163–170 (2018). (PMID: 2925172010.1038/nchembio.2538)
Cantley, J. et al. Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers. Nat Commun. 13, 6814 (2022).
Gopalsamy, A. Selectivity through targeted protein degradation (TPD). J. Med. Chem. 65, 8113–8126 (2022). (PMID: 3565842810.1021/acs.jmedchem.2c00397)
Toriki, E. S. et al. Rational chemical design of molecular glue degraders. Cent. Sci. 9, 915–926 (ACS, 2023).
Sakuma, T., Nakade, S., Sakane, Y., Suzuki, K. I. T. & Yamamoto, T. MMEJ-assisted gene knock-in using TALENs and CRISPR-Cas9 with the PITCh systems. Nat. Protoc. 11, 118–133 (2016). (PMID: 2667808210.1038/nprot.2015.140)
Shi, J. et al. Discovery of cancer drug targets by CRISPR–Cas9 screening of protein domains. Nat. Biotechnol. 33, 661–667 (2015). (PMID: 25961408452999110.1038/nbt.3235)
Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat. Biotechnol. 34, 184–191 (2016). (PMID: 26780180474412510.1038/nbt.3437)
Brinkman, E. K., Chen, T., Amendola, M. & Van Steensel, B. Easy quantitative assessment of genome editing by sequence trace decomposition. Nucleic Acids Res. 42, e168 (2014). (PMID: 25300484426766910.1093/nar/gku936)
Neumann, T. et al. Quantification of experimentally induced nucleotide conversions in high-throughput sequencing datasets. BMC Bioinf. 20, 258 (2019). (PMID: 10.1186/s12859-019-2849-7)
Corces, M. R. et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat. Methods 14, 959–962 (2017). (PMID: 28846090562310610.1038/nmeth.4396)
Subramanian, A. et al. Gene set enrichment analysis:na knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005). (PMID: 16199517123989610.1073/pnas.0506580102)
Mootha, V. K. et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273 (2003). (PMID: 1280845710.1038/ng1180)
معلومات مُعتمدة: DP5 OD026380 United States OD NIH HHS; K08 CA245251 United States CA NCI NIH HHS
المشرفين على المادة: EC 3.5.1.98 (Mi-2 Nucleosome Remodeling and Deacetylase Complex)
EC 3.5.1.98 (Histone Deacetylase 1)
0 (Nucleosomes)
EC 3.5.1.98 (HDAC1 protein, human)
EC 3.5.1.98 (HDAC2 protein, human)
EC 3.5.1.98 (Histone Deacetylase 2)
تواريخ الأحداث: Date Created: 20230724 Date Completed: 20230823 Latest Revision: 20240504
رمز التحديث: 20240504
مُعرف محوري في PubMed: PMC10529074
DOI: 10.1038/s41594-023-01041-4
PMID: 37488358
قاعدة البيانات: MEDLINE
الوصف
تدمد:1545-9985
DOI:10.1038/s41594-023-01041-4