Alexander J. Ruthenburg

Associate Professor
Research Summary
The unifying theme of my lab is the elucidation of molecular mechanisms underlying management chromatin, the physiological form of the genome. In particular, we are interested in how post translational modifications to histones, newly appreciated DNA modifications and noncoding RNA can control chromatin structure. Our research spans several traditional disciplines, ranging from discovery biochemistry and genome-scale measurements to mechanistic characterization with biophysical methods coupled with X-Ray structure to address fundamental questions in chromatin biology. We have pioneered new technologies to make quantitative local measurements of chromatin components. Projects ideally will transition from discovery biology to detailed molecular and structural investigation.
Chromatin, Epigenetics, Biochemistry, Genomics, Regulation of Gene Expression, Chromatin Immunoprecipitation, Chromatin Associated RNA, Epigenomics, Epigenetic Process, Transcriptional Activation, Nucleosomes
  • Rockefeller University , New York, NY, Postdoctoral Fellow Chromatin biochemsitry and epigenetics 8/2010
  • Harvard University , Cambridge, MA, Ph.D. Chemical and Structural biology 9/2005
  • Carleton College, Northfield, MN, B.A. Chemistry 6/1999
Awards & Honors
  • 2000 - 2004 National Science Foundation Graduate Research Fellow Harvard University
  • 2007 - 2010 Irvington Institute Research Fellowship Cancer Research Institute
  • 2010 - 2012 Junior Investigator Chicago Biomedical Consortium
  • 2010 - 2015 Neubauer Family Foundation Assistant Professor University of Chicago
  • 2011 - Kavli Fellow National Academy of Sciences
  • 2013 - 2017 New Scholar in Aging Ellison Medical Foundation
  1. Charles David Allis (1951-2023). Nat Genet. 2023 Apr; 55(4):522-523. View in: PubMed

  2. Specificity Guides Interpretation: On H3K4 Methylation at Enhancers and Broad Promoters. bioRxiv. 2023 Jan 17. View in: PubMed

  3. Profiling lariat intermediates reveals genetic determinants of early and late co-transcriptional splicing. Mol Cell. 2022 Nov 21. View in: PubMed

  4. Non-canonical H3K79me2-dependent pathways promote the survival of MLL-rearranged leukemia. Elife. 2021 07 15; 10. View in: PubMed

  5. Sequence deeper without sequencing more: Bayesian resolution of ambiguously mapped reads. PLoS Comput Biol. 2021 04; 17(4):e1008926. View in: PubMed

  6. Epigenetic homogeneity in histone methylation underlies sperm programming for embryonic transcription. Nat Commun. 2020 07 13; 11(1):3491. View in: PubMed

  7. Chromatin-enriched RNAs mark active and repressive cis-regulation: An analysis of nuclear RNA-seq. PLoS Comput Biol. 2020 02; 16(2):e1007119. View in: PubMed

  8. Native internally calibrated chromatin immunoprecipitation for quantitative studies of histone post-translational modifications. Nat Protoc. 2019 12; 14(12):3275-3302. View in: PubMed

  9. A Mutation in Histone H2B Represents a New Class of Oncogenic Driver. Cancer Discov. 2019 10; 9(10):1438-1451. View in: PubMed

  10. Examining the Roles of H3K4 Methylation States with Systematically Characterized Antibodies. Mol Cell. 2018 10 04; 72(1):162-177.e7. View in: PubMed

  11. Regulated Capture of V? Gene Topologically Associating Domains by Transcription Factories. Cell Rep. 2018 08 28; 24(9):2443-2456. View in: PubMed

  12. Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy. Cancer Discov. 2018 11; 8(11):1376-1389. View in: PubMed

  13. Facile target validation in an animal model with intracellularly expressed monobodies. Nat Chem Biol. 2018 09; 14(9):895-900. View in: PubMed

  14. Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm. Elife. 2017 12 27; 6. View in: PubMed

  15. Quantitative and Structural Assessment of Histone Methyllysine Analogue Engagement by Cognate Binding Proteins Reveals Affinity Decrements Relative to Those of Native Counterparts. Biochemistry. 2018 01 23; 57(3):300-304. View in: PubMed

  16. Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription. Nat Struct Mol Biol. 2017 Jul; 24(7):596-603. View in: PubMed

  17. Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation. Proc Natl Acad Sci U S A. 2016 Feb 23; 113(8):2092-7. View in: PubMed

  18. Nuclear Fractionation Reveals Thousands of Chromatin-Tethered Noncoding RNAs Adjacent to Active Genes. Cell Rep. 2015 Aug 18; 12(7):1089-98. View in: PubMed

  19. An Interactive Database for the Assessment of Histone Antibody Specificity. Mol Cell. 2015 Aug 06; 59(3):502-11. View in: PubMed

  20. Calibrating ChIP-Seq with Nucleosomal Internal Standards to Measure Histone Modification Density Genome Wide. Mol Cell. 2015 Jun 04; 58(5):886-99. View in: PubMed

  21. Traceless semisynthesis of a set of histone 3 species bearing specific lysine methylation marks. Chembiochem. 2014 Sep 22; 15(14):2071-5. View in: PubMed

  22. Recombinant antibodies to histone post-translational modifications. Nat Methods. 2013 Oct; 10(10):992-5. View in: PubMed

  23. Validation of histone-binding partners by peptide pull-downs and isothermal titration calorimetry. Methods Enzymol. 2012; 512:187-220. View in: PubMed

  24. Does activation of the anti proton, rather than concertedness, determine the stereochemistry of base-catalyzed 1,2-elimination reactions? Anti stereospecificity in E1cB eliminations of ?-3-trifluoromethylphenoxy esters, thioesters, and ketones. J Org Chem. 2012 Mar 16; 77(6):2819-28. View in: PubMed

  25. The United States of histone ubiquitylation and methylation. Mol Cell. 2011 Jul 08; 43(1):5-7. View in: PubMed

  26. Recognition of a mononucleosomal histone modification pattern by BPTF via multivalent interactions. Cell. 2011 May 27; 145(5):692-706. View in: PubMed

  27. Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. Mol Cell. 2010 Jun 25; 38(6):853-63. View in: PubMed

  28. Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol. 2007 Dec; 8(12):983-94. View in: PubMed

  29. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol. 2007 Nov; 14(11):1025-1040. View in: PubMed

  30. Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell. 2007 Jan 12; 25(1):15-30. View in: PubMed

  31. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol. 2006 Aug; 13(8):713-9. View in: PubMed

  32. Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex. Nat Struct Mol Biol. 2006 Aug; 13(8):704-12. View in: PubMed

  33. Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNA. Nat Struct Mol Biol. 2006 Feb; 13(2):153-9. View in: PubMed

  34. Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase. J Biol Chem. 2005 Nov 04; 280(44):37041-7. View in: PubMed

  35. A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal domain imparts unidirectional supercoiling bias. J Biol Chem. 2005 Jul 15; 280(28):26177-84. View in: PubMed