Chromatin is the physiologic form of the genome. Rather than mere packaging, chromatin structure appears to serve as the master regulator of underlying DNA function. Local chromatin structure may be stable for decades, yet is sufficiently dynamic to respond to signaling pathways, potentiating transcriptional program changes in development. Indeed cellular identity and changes thereof are intimately connected to chromatin states -- keeping a neuron a neuron and not a liver cell. What are the molecular mechanisms factors that control chromatin structure?
The unifying theme of our lab is the elucidation of molecular mechanisms underlying genome management using the toolkits of biochemistry, chemical and structural biology; in particular, we are interested in how posttranslational modifications and noncoding RNA can control chromatin structure. Our research spans several traditional disciplines, ranging from discovery biochemistry and chemical biology to mechanistic characterization with biophysical methods coupled with X-Ray structure to address fundamental questions in chromatin biology. Projects ideally will transition from discovery biology to detailed molecular and structural investigation.
Kathryn Malecek, Alexander J. Ruthenburg. Validation of histone-binding partners by peptide pull-downs and isothermal titration calorimetry. Methods in Enzymolology 512:187-220. (2012). (PubMed)
Michael Werner, Alexander J. Ruthenburg. The United States of histone ubiquitylation and methylation. Mol. Cell, 43: 5–7 (2011). (PubMed)
Alexander J. Ruthenburg, Haitao Li, Thomas A. Milne, Yali Dou, Scott Dewell, Robert K. McGinty, Melanie Yuen, Beatrix Ueberheide, Tom W. Muir, Dinshaw J. Patel, C. David Allis. Recognition of a mononucleosomal histone modification pattern by BPTF via multivalent interactions. Cell 145: 692-706 (2011). (PubMed)
Thomas A. Milne, Jaehoon Kim, Gang G. Wang, Sonja Stadler, Sarah J. Whitcomb, Venkatesha Basrur, Alexander J. Ruthenburg, Kojo S. Elenitoba-Johnson, Robert G. Roeder, C. David Allis. Multivalent interactions of the MLL1 PHD fingers and CXXC domain control recruitment and stable binding of MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. Mol. Cell, 38: 853-863 (2010). (PubMed)
Alexander J. Ruthenburg, Haitao Li, Dinshaw J. Patel, C. David Allis. Multivalent engagement of chromatin modifications by linked binding modules. Nat. Rev. Mol. Cell Biol. 8: 983-94 (2007). (PubMed)
Sean D. Taverna, Haitao Li, Alexander J. Ruthenburg, C. David Allis, Dinshaw J. Patel. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat. Struct. Mol. Biol. 14: 1025-40 (2007). (PubMed)
Alexander J. Ruthenburg, C. David Allis, Joanna Wysocka. Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol. Cell. 25: 15-30 (2007). (PubMed)
Alexander J. Ruthenburg, Wooikoon Wang, Daina M. Graybosch, Haitao Li, C. David Allis, Dinshaw J. Patel, Gregory L. Verdine. Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex. Nat. Struct. Mol. Biol. 13: 704-712 (2006). (PubMed)
Yali Dou, Thomas A. Milne, Alexander J. Ruthenburg, Seunghee Lee, Jae W. Lee, Gregory L. Verdine, C. David Allis, Robert G. Roeder. Regulation of MLL1 H3 K4 Methyltransferase Activity by its Core Components. Nat. Struct. Mol. Biol. 13: 713-719 (2006). (PubMed)