العلوم والتكنولوجيا

بروتينا قراءة الهستونات MLLT1 وMLLT3 يركّزان AID لمنحه خصوصية موضعية

  • Lauring, M. C. & Basu, U. Somatic hypermutation mechanisms during lymphomagenesis and transformation. Curr. Opin. Genet. Dev. 85, 102165 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Robbiani, D. F. et al. AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations. Mol. Cell 36, 631–641 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bal, E. et al. Super-enhancer hypermutation alters oncogene expression in B cell lymphoma. Nature 607, 808–815 (2022).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Leeman-Neill, R. J. et al. Noncoding mutations cause super-enhancer retargeting resulting in protein synthesis dysregulation during B cell lymphoma progression. Nat. Genet. 55, 2160–2174 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Feng, Y., Seija, N., Di Noia, J. M. & Martin, A. AID in antibody diversification: there and back again. Trends Immunol. 41, 586–600 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yeap, L. S. & Meng, F.-L. Cis– and trans-factors affecting AID targeting and mutagenic outcomes in antibody diversification. Adv. Immunol. 141, 51–103 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Yamane, A. et al. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nat. Immunol. 12, 62–69 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Matthews, A. J., Husain, S. & Chaudhuri, J. Binding of AID to DNA does not correlate with mutator activity. J. Immunol. 193, 252–257 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Methot, S. P. et al. A licensing step links AID to transcription elongation for mutagenesis in B cells. Nat. Commun. 9, 1248 (2018).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Qin, Y. & Meng, F.-L. Taming AID mutator activity in somatic hypermutation. Trends Biochem. Sci. 49, 622–632 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Pavri, R. et al. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 143, 122–133 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Willmann, K. L. et al. A role for the RNA Pol II-associated PAF complex in AID-induced immune diversification. J. Exp. Med. 209, 2099–2111 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dai, P. et al. Transcription-coupled AID deamination damage depends on ELOF1-associated RNA polymerase II. Mol. Cell 85, 1280–1295.e9 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wu, L. et al. Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination. Mol. Cell 85, 1296–1310.e7 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Begum, N. A., Stanlie, A., Nakata, M., Akiyama, H. & Honjo, T. The histone chaperone Spt6 is required for activation-induced cytidine deaminase target determination through H3K4me3 regulation. J. Biol. Chem. 287, 32415–32429 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, L., Whang, N., Wuerffel, R. & Kenter, A. L. AID-dependent histone acetylation is detected in immunoglobulin S regions. J. Exp. Med. 203, 215–226 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kuang, F. L., Luo, Z. & Scharff, M. D. H3 trimethyl K9 and H3 acetyl K9 chromatin modifications are associated with class switch recombination. Proc. Natl Acad. Sci. USA 106, 5288–5293 (2009).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, Q. et al. Epigenetic targeting of activation-induced cytidine deaminase. Proc. Natl Acad. Sci. USA 111, 18667–18672 (2014).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pefanis, E. et al. Noncoding RNA transcription targets AID to divergently transcribed loci in B cells. Nature 514, 389–393 (2014).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Basu, U. et al. The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell 144, 353–363 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Meng, F.-L. et al. Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability. Cell 159, 1538–1548 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Qian, J. et al. B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity. Cell 159, 1524–1537 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Subramani, P. G. et al. DOT1L activity limits transcription elongation velocity and favors RNAPII pausing to facilitate mutagenesis by AID. Nat. Commun. 17, 1623 (2026).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, Z., Xu, J., Liu, J., Wang, J. & Lei, L. SEC: a core hub during cell fate alteration. FASEB J. 38, e23680 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Aoi, Y. & Shilatifard, A. Transcriptional elongation control in developmental gene expression, aging, and disease. Mol. Cell 83, 3972–3999 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lin, C. et al. Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC). Genes Dev. 25, 1486–1498 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tsukumo, S.-I. et al. AFF3, a susceptibility factor for autoimmune diseases, is a molecular facilitator of immunoglobulin class switch recombination. Sci. Adv. 8, eabq0008 (2022).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, Y. et al. AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation. Cell 159, 558–571 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wan, L. et al. ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia. Nature 543, 265–269 (2017).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ramiro, A. R. et al. Role of genomic instability and p53 in AID-induced c-Myc-Igh translocations. Nature 440, 105–109 (2006).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rada, C. A., Di Noia, J. M. & Neuberger, M. S. Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation. Mol. Cell 16, 163–171 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wu, L. et al. HMCES protects immunoglobulin genes specifically from deletions during somatic hypermutation. Genes Dev. 36, 433–450 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Arakawa, H., Saribasak, H. & Buerstedde, J.-M. Activation-induced cytidine deaminase initiates immunoglobulin gene conversion and hypermutation by a common intermediate. PLoS Biol. 2, E179 (2004).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • He, N. et al. Human polymerase-associated factor complex (PAFc) connects the super elongation complex (SEC) to RNA polymerase II on chromatin. Proc. Natl Acad. Sci. USA 108, E636–E645 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Zahn, A. et al. Activation induced deaminase C-terminal domain links DNA breaks to end protection and repair during class switch recombination. Proc. Natl Acad. Sci. USA 111, E988–E997 (2014).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Erb, M. A. et al. Transcription control by the ENL YEATS domain in acute leukaemia. Nature 543, 270–274 (2017).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Peycheva, M. et al. DNA replication timing directly regulates the frequency of oncogenic chromosomal translocations. Science 377, eabj5502 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Longerich, S., Tanaka, A., Bozek, G., Nicolae, D. & Storb, U. The very 5′ end and the constant region of Ig genes are spared from somatic mutation because AID does not access these regions. J. Exp. Med. 202, 1443–1454 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rada, C. & Milstein, C. The intrinsic hypermutability of antibody heavy and light chain genes decays exponentially. EMBO J. 20, 4570–4576 (2001).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Heltzel, J. H. M., Maul, R. W., Yang, W. & Gearhart, P. J. Promoter proximity defines mutation window for VH and VΚ genes rearranged to different J genes. J. Immunol. 208, 2220–2226 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Duan, Z. et al. Role of Dot1L and H3K79 methylation in regulating somatic hypermutation of immunoglobulin genes. Proc. Natl Acad. Sci. USA 118, e2104013118 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mueller, D. et al. A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 110, 4445–4454 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wan, L. et al. Impaired cell fate through gain-of-function mutations in a chromatin reader. Nature 577, 121–126 (2020).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar 

  • Zeisig, D. T. et al. The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners with chromatin. Oncogene 24, 5525–5532 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Song, L. et al. Hotspot mutations in the structured ENL YEATS domain link aberrant transcriptional condensates and cancer. Mol. Cell 82, 4080–4098.e12 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ui, A., Nagaura, Y. & Yasui, A. Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair. Mol. Cell 58, 468–482 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hetzner, K., Garcia-Cuellar, M.-P., Büttner, C. & Slany, R. K. The interaction of ENL with PAF1 mitigates polycomb silencing and facilitates murine leukemogenesis. Blood 131, 662–673 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Guo, C. et al. ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation. Sci. Adv. 6, eaay4858 (2020).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Budinich, K. A. et al. RNA reinforces condensate nucleation on chromatin to amplify oncogenic transcription. Mol. Cell https://doi.org/10.1016/j.molcel.2026.05.024 (2026).

    Article 
    PubMed 

    Google Scholar 

  • Methot, S. P. et al. Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm. J. Exp. Med. 212, 581–596 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Larijani, M. et al. AID associates with single-stranded DNA with high affinity and a long complex half-life in a sequence-independent manner. Mol. Cell. Biol. 27, 20–30 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Rouaud, P. et al. The IgH 3′ regulatory region controls somatic hypermutation in germinal center B cells. J. Exp. Med. 210, 1501–1507 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang, J. et al. MYC phase separation selectively modulates the transcriptome. Nat. Struct. Mol. Biol. 31, 1567–1579 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bremer, A. et al. Reconciling competing models on the roles of condensates and soluble complexes in transcription factor function. Mol. Cell 85, 2718–2732.e7 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Xie, X. et al. C-terminal deletion-induced condensation sequesters AID from IgH targets in immunodeficiency. EMBO J. 41, e109324 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • King, J. J. & Larijani, M. Structural plasticity of substrate selection by activation-induced cytidine deaminase as a regulator of its genome-wide mutagenic activity. FEBS Lett. 595, 3–13 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mikhova, M. et al. A dynamic RNA hub facilitates activation-induced cytidine deaminase recruitment to the immunoglobulin heavy-chain locus. Mol. Cell https://doi.org/10.1016/j.molcel.2026.06.012 (2026).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wu, L. et al. Transcription pause and elongation regulators mediate somatic hypermutation. Nature https://doi.org/10.1038/s41586-026-11092-4 (2026).

  • Kenter, A. L. et al. Three-dimensional architecture of the IgH locus facilitates class switch recombination. Ann. N. Y. Acad. Sci. 1267, 86–94 (2012).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Haque, F., Honjo, T. & Begum, N. A. XLID syndrome gene Med12 promotes Ig isotype switching through chromatin modification and enhancer RNA regulation. Sci. Adv. 8, eadd1466 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yeap, L.-S. et al. Sequence-intrinsic mechanisms that target AID mutational outcomes on antibody genes. Cell 163, 1124–1137 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nakamura, M. et al. High frequency class switching of an IgM+ B lymphoma clone CH12F3 to IgA+ cells. Int. Immunol. 8, 193–201 (1996).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shanbhag, N. M., Rafalska-Metcalf, I. U., Balane-Bolivar, C., Janicki, S. M. & Greenberg, R. A. ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. Cell 141, 970–981 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Moustakim, M. et al. Discovery of an MLLT1/3 YEATS domain chemical probe. Angew. Chem. Int. Ed. Engl. 57, 16302–16307 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Raux, B. et al. Discovery of PFI-6, a small-molecule chemical probe for the YEATS domain of MLLT1 and MLLT3. Bioorg. Med. Chem. Lett. 98, 129546 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gurumurthy, C. B. et al. Creation of CRISPR-based germline-genome-engineered mice without ex vivo handling of zygotes by i-GONAD. Nat. Protoc. 14, 2452–2482 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Modzelewski, A. J. et al. Efficient mouse genome engineering by CRISPR-EZ technology. Nat. Protoc. 13, 1253–1274 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Casola, S. et al. Tracking germinal center B cells expressing germ-line immunoglobulin 1 transcripts by conditional gene targeting. Proc. Natl Acad. Sci. USA 103, 7396–7401 (2006).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nojima, T. et al. In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo. Nat. Commun. 2, 465 (2011).

    Article 
    ADS 
    PubMed 

    Google Scholar 

  • Caeser, R. et al. Genetic modification of primary human B cells to model high-grade lymphoma. Nat. Commun. 10, 4543 (2019).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ling, A. K. et al. Double-stranded DNA break polarity skews repair pathway choice during intrachromosomal and interchromosomal recombination. Proc. Natl Acad. Sci. USA 115, 2800–2805 (2018).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Arakawa, H., Hauschild, J. & Buerstedde, J.-M. Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion. Science 295, 1301–1306 (2002).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar 

  • Sawasdichai, A., Chen, H.-T., Abdul Hamid, N., Jayaraman, P.-S. & Gaston, K. In situ subcellular fractionation of adherent and non-adherent mammalian cells. J. Vis. Exp. https://doi.org/10.3791/1958 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Craig, R. & Beavis, R. C. TANDEM: matching proteins with tandem mass spectra. Bioinformatics 20, 1466–1467 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shteynberg, D. et al. iProphet: multi-level integrative analysis of shotgun proteomic data improves peptide and protein identification rates and error estimates. Mol. Cell. Proteomics 10, M111.007690 (2011).

  • Liu, G. et al. ProHits: integrated software for mass spectrometry-based interaction proteomics. Nat. Biotechnol. 28, 1015–1017 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Keller, A., Nesvizhskii, A. I., Kolker, E. & Aebersold, R. Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal. Chem. 74, 5383–5392 (2002).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar 

  • Nesvizhskii, A. I., Keller, A., Kolker, E. & Aebersold, R. A statistical model for identifying proteins by tandem mass spectrometry. Anal. Chem. 75, 4646–4658 (2003).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar 

  • Teo, G. et al. SAINTexpress: improvements and additional features in Significance Analysis of Interactome software. J. Proteomics 100, 37–43 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Egan, B. et al. An alternative approach to ChIP-seq normalization enables detection of genome-wide changes in histone H3 lysine 27 trimethylation upon EZH2 inhibition. PLoS ONE 11, e0166438 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ewels, P., Magnusson, M., Lundin, S. & Käller, M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics 32, 3047–3048 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ramírez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160–W165 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gaspar, J. M. Improved peak-calling with MACS2. Preprint at bioRxiv https://doi.org/10.1101/496521 (2018).

  • Yu, G., Wang, L.-G. & He, Q.-Y. ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization. Bioinformatics 31, 2382–2383 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gregersen, L. H., Mitter, R. & Svejstrup, J. Q. Using TTchem-seq for profiling nascent transcription and measuring transcript elongation. Nat. Protoc. 15, 604–627 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lawrence, M. et al. Software for computing and annotating genomic ranges. PLoS Comput. Biol. 9, e1003118 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gressel, S. et al. CDK9-dependent RNA polymerase II pausing controls transcription initiation. eLife 6, e29736 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Velychko, T. et al. CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release. Mol. Cell 84, 2287–2303.e10 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Faust, G., Stand, A. & Weuster-Botz, D. IPTG can replace lactose in auto-induction media to enhance protein expression in batch-cultured Escherichia coli. Eng. Life Sci. 15, 824–829 (2015).

    Article 
    CAS 

    Google Scholar 

  • Freibaum, B. D., Messing, J., Yang, P., Kim, H. J. & Taylor, J. P. High-fidelity reconstitution of stress granules and nucleoli in mammalian cellular lysate. J. Cell Biol. 220, e202009079 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stirling, D. R.et al. CellProfiler 4: improvements in speed, utility and usability. BMC Bioinformatics 22, 433 (2021).

  • Mészáros, B., Erdős, G. & Dosztányi, Z. IUPred2A: context-dependent prediction of protein disorder as a function of redox state and protein binding. Nucleic Acids Res. 46, W329–W337 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

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