In Memory of Susan Abmayr 1956-2019
Susan Abmayr, Ph.D.
Associate Professor, Department of Anatomy & Cell Biology
The University of Kansas School of Medicine
Ph.D., Biochemistry and Molecular Biology
B.S., Biological Sciences
Protein Complexes that Modify Chromatin and Regulate Gene Transcription:
Within a cell, transcription of DNA packaged into chromatin is regulated by large multiprotein complexes that modify chromatin structure and gene accessibility through a variety of mechanisms. Current interests focus on the biochemical properties and in vivo requirements for these complexes. In particular, we take advantage of model organisms that include the fruit fly Drosophila melanogaster, and cultured cells from both Drosophila and mammals to examine composition, binding patterns and patterns of gene expression.
One of the complexes under investigation is the highly conserved SAGA complex, which includes more than 18 subunits that are organized into 4 distinct protein modules. These modules mediate its binding within chromatin and its ability to modify histones. It includes two enzymatic activities: a histone acetyltransferase (HAT) and a deubiquitinase (DUB). Through the use of Drosophila mutations and RNAi knock down strategies we are examining the biological requirements for each of these enzymatic activities and associated subunits. We seek to address whether the four protein modules present in the SAGA complex are equally required by all genes and, moreover, whether the submodules have functions independent of SAGA. Initial studies that focused on oogenesis and early embryonic development have indeed revealed that different modules regulate overlapping and exclusive sets of genes, and that loss/knockdown of different subunits results in strikingly different phenotypes and patterns of gene expression. In particular, the HAT-containing module of SAGA plays a critical role in germline development and oogenesis. Somewhat surprisingly, the DUB module is not required for this process or for expression of many oogenesis-specific genes.
Interestingly, genome-wide studies also revealed that some SAGA subunits are present at promoters independent of the HAT module. Future interests include whether these subunits are present in other chromatin modifying complexes and what types of genes/promoters are bound by these novel complexes.
Another active area of research in our lab focuses on a second chromatin modifying complex, the ATP-dependent Swi/Snf chromatin remodeling complex. Mutations in many of the subunits of this complex are associated with altered cell behavior and cancers. Studies in yeast have recently shown that this complex is also modular in nature, and revealed that some submodules remain stable when other subunits are lost through mutation, and retain their DNA binding properties. Current efforts are addressing whether the mammalian Swi/Snf complex is organized and behaves in a similar manner. The overlying goals of these studies are to determine whether stable subunits present in these cell lines associate with novel proteins, how these are modified by cancer-causing mutations, and whether the presence of mutant Swi/Snf complexes can interfere with the functioning of normal SAGA. Through these efforts, we hope to uncover mechanisms through which Swi/Snf contributes to altered growth properties associated with cancer.
Organogenesis: Integration of cell-cell interactions, intracellular signaling cascades, and changing patterns of gene expression to generate differentiated tissues.
During the development of multicellular organisms, cells acquire specific properties and capabilities associated with their ultimate purpose in the body, and organize themselves into functional structures. For over 20 years, my laboratory explored critical developmental steps in the differentiation of myoblasts and the generation of muscle fibers. Contributions ranged from the identification of transcription factors such as the MADS-box containing Mef2 protein, which regulates genes associated with overt muscle function such as myosin and plays a broad role in driving myoblasts to more differentiated states to Midline, a T-box transcription factor that specifies the unique developmental program of specific muscle fibers. Our studies also extended to the myoblast cell surface, and included the discovery of the IgSF protein SNS and the Rac1 regulatory complex MBC/Ced12, some of the earliest identified Drosophila genes critical for fusion of myoblasts into myotubes. These proteins mediate recognition and adhesion between myoblasts and regulation of actin-associated processes that occur at the point of cell fusion.
Elgin, S.C.R., Abmayr, S.M., Cartwright, I.L., Howard, G.C., Keene, M.A., Lowenhaupt, K., Wong, Y-C., Wu, C. 1979. Chromatin structure and gene expression in Drosophila. Gene Structure and Expression (D.H. Dean, L.F. Johnson, P.C. Kimball, and P.S. Perlman, Eds.) Ohio State University Press, Columbus. p 305-332. Abstract
Howard, G.C., Abmayr, S.M., Shinefeld, L.A., Sato, V.L., Elgin, S.C.R. 1981. Monoclonal antibodies against specific nonhistone chromosomal proteins of Drosophila correlated with gene activity. J. Cell Biol. 88, 219-227. Abstract
Cartwright, I.L., Keene, M.A., Howard, G.C., Abmayr, S.M, Fleischmann, G., Lowenhaupt, K., Elgin, S.C.R. 1982. Chromatin structure and gene activity: The role of nonhistone chromosomal proteins. Critical Reviews in Biochemistry, CRC Press. 13, 1-26. Abstract
Hill, R.J., Mott, M.R., Burnett, E.J., Abmayr, S.M, Lowenhaupt, K., Elgin, S.C.R. 1982. Nucleosome repeat structure is present in native salivary chromosomes of Drosophila melanogaster. J. Cell Biol. 95, 262-269. Abstract
Abmayr, S.M., Feldman, L.D., Roeder, R.G. 1985. In vitro stimulation of specific RNA polymerase II-mediated transcription by the pseudorabies virus immediate early protein. Cell. 43, 821-829. Abstract
Abmayr, S.M., Workman, J.L., Roeder, R.G. 1988. The pseudorabies immediate early protein stimulates in vitro transcription by facilitating TFIID: promoter interactions. Genes Dev. 2, 542-553. Abstract
Workman, J.L., Abmayr, S.M., Cromlish, W.A., Roeder, R.G. 1988. Transcriptional regulation by the immediate early protein of pseudorabies virus during in vitro nucleosome assembly. Cell. 55, 211-219. Abstract
Abmayr, S.M., Reed, R., Maniatis, T. 1988. Identification of a functional mammalian spliceosome containing un-spliced pre-mRNA. Proc. Natl. Acad. Sci. 85, 7216-7220. Abstract
Cromlish, W.A., Abmayr, S.M., Workman, J.L., Horikoshi, M., Roeder, R.G. 1989. Transcriptionally active immediate early protein of pseudorabies virus binds to specific sites on class II gene promoters. J. Virol. 63, 1869-1876 Abstract
Abmayr, S.M., Workman, J.L. 1990. Preparation of nuclear extracts from cultured cells. Current Protocols in Molecular Biology. (F.M. Ausubel, R. Brent, R.E. Kingston, D.D. Moore, J.G. Siedman, J.A. Smith, and K. Struhl, Eds.) Greene Publishing Associates/Wiley Interscience, New York. (Supplement 11).
Michelson, A.M.*, Abmayr, S.M.*, Bate, C.M., Martinez Arias, A., Maniatis, T. 1990. Expression of a MyoD family member prefigures muscle pattern in Drosophila embryos. Genes Dev. 4, 2086-2097. *The first two authors contributed equally to this work. Abstract
Corbin, V., Michelson, A.M., Abmayr, S.M., Neel, V., Alcamo, E., Maniatis, T., Young, M.W. 1991. A role for the Drosophila neurogenic genes in mesoderm differentiation. Cell. 67, 311-323. Abstract
Abmayr, S.M., Michelson, A.M., Corbin, V., Young, M.W., Maniatis, T. 1992. nautilus, a Drosophila member of the myogenic regulatory gene family. Gene Expression and Neuromuscular Development. Keystone Symposium Proceedings Series. (H. Blau and A. Kelly, Eds.) Raven Press, New York. p 1-16.
Abmayr, S.M., Workman, J.L. 1992. Preparation of nuclear extracts from cultured cells. Short Protocols in Molecular Biology. (F.M. Ausubel, R. Brent, R.E. Kingston, D.D. Moore, J.G. Siedman, J.A. Smith, and K. Struhl, Eds.) Greene Publishing Associates/Wiley Interscience, New York. p 12.3-12.5.
Nguyen, H.T., Bodmer, R., Abmayr, S.M., McDermott, J.C., Spoerel, N.A. 1994. D-mef2: A Drosophila mesoderm-specific MADS box-containing gene with a biphasic expression profile during embryogenesis. Proc. Natl. Acad. Sci. USA. 91, 7520-7524. Abstract
Abmayr, S.M., Erickson, M.S., Bour, B.A. 1995. Embryonic development of the larval body wall musculature of Drosophila. Trends Genet. 11, 153-159. Abstract
Bour, B.A., O'Brien, M.A., Lockwood, W.L., Goldstein, E.S., Bodmer, R., Taghert, P.H., Abmayr, S.M., Nguyen, H. T. 1995. Drosophila MEF2, a transcription factor that is essential for myogenesis. Genes Dev. 9, 730-741. Abstract
Rushton, E., Drysdale, R., Abmayr, S.M., Michelson, A.M., Bate, M. 1995. Mutations in a novel gene, myoblast city, provide evidence in support of the founder cell hypothesis for Drosophila muscle development. Development. 121, 1979-1988. Abstract
Keller, C.A., Erickson, M.S., Abmayr, S.M. 1997. Misexpression of nautilus induces myogenesis in cardioblasts and alters the pattern of somatic muscle fibers. Dev. Biol. 181, 197-212. Abstract
Lin, M-H., Bour, B.A., Abmayr, S.M., Storti, R.V. 1997. Ectopic expression of MEF2 in the epidermis induces epidermal expression of muscle genes and abnormal muscle development in Drosophila. Dev. Biol. 182, 240-255. Abstract
Erickson, M.R.S., Galletta, B.J., Abmayr, S.M. 1997. Drosophila mbc encodes a conserved protein that is essential for myoblast fusion, dorsal closure and cytoskeletal organization. J. Cell Biol. 138, 589-603.
Abmayr, S.M., Keller, C.A. 1998. Drosophila myogenesis, and insights into the role of nautilus. Curr. Topics Dev. Biol. 38, 35-80. Abstract
Keller, C.A., Grill, M.A., Abmayr, S.M. 1998. A role for nautilus in the differentiation of muscle precursors. Dev. Biol. 202, 157-171. Abstract
Galletta, B.J., Niu, X-P., Erickson, M.R.S., S.M. Abmayr, S.M. 1999. Identification of a Drosophila homologue to Crk by interaction with MBC. Gene. 228, 243-252. Abstract
Bour, B.A., Chakravarti, M., West, J., Abmayr, S.M. 2000. Drosophila SNS, a member of the immunoglobulin superfamily that is essential for myoblast fusion. Genes Dev. 14, 1498-1511. Abstract
Balagopalan, L., Keller, C.A., Abmayr, S.M. 2001. Loss-of-function mutations reveal that the Drosophila nautilus gene is not essential for embryonic myogenesis or viability.Dev. Biol. 231, 374-382. Abstract
Abmayr, S.M., Corroza, M., Workman, J. L. 2001. Preparation of nuclear extracts from cultured cells. Current Protocols in Pharmacology.(S.J. Enna, M. Williams, J.W. Ferkany, T. Kenakin, P. Moser and B. Ruggeri, Eds.) John Wiley and Sons, Hoboken. Abstract
Abmayr, S.M., Balagopalan, L., Galletta, B.J., Hong, S-J. 2003. Cell and Molecular Biology of Myoblast Fusion. International Review Cytology. 225, 33-89. Abstract
Kusch, T., Guelman, S., Abmayr, S.M., Workman, J.L. 2003. Two Drosophila Ada2 homologues function in different multiprotein complexes. Mol. Cell. Biol. 23, 3305-3319. Abstract
Presgraves, D.C., Balagopalan, L., Abmayr, S.M., Orr, H.A. 2003. Adaptive evolution drives divergence of a hybrid inviability gene in Drosophila. Nature. 423, 715-719. Abstract
Abmayr, S.M., Workman, J.L. 2003. Transcription factors prominently in Lasker award to Roeder. Cell. 115, 1-4. (Essay). Abstract
Workman, J.L., Abmayr, S.M. 2004. Histone H3 variants and modifications on transcribed genes. Proc. Natl. Acad. Sci. USA. 101, 1429-1430. (Commentary). Abstract
Kusch, T., Florens, L., Macdonald, W.H., Swanson, S.K., Glaser, R.L., Yates, J.R., Abmayr, S.M., Washburn, M.P., Workman, J.L. 2004. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science. 306, 2084-2087. Abstract
Galletta, B.J., Banerje, R., Chakravarti, M., Abmayr, S.M. 2004. Functional analysis of the SNS protein in embryos and cultured cells reveals that the SNS cytodomain is expendable for cell adhesion but is essential for myoblast migration and fusion. Mech. Dev. 121, 1455-1468. Abstract
Abmayr, S.M., Balagopalan, L., Galletta, B.J., Hong, S-J. 2005. Myogenesis and Muscle Development. Comprehensive Molecular Insect Science. (L. Gilbert, K. Iatrou and S. Gill, Eds.) Elsevier Ltd., Oxford. p 1-43.
Abmayr, S.M., Kocherlakota, K.S. 2005. Muscle Morphogenesis: The process of embryonic myoblast fusion. Muscle Development in Drosophila. (H. Sink, Ed.) Landes Bioscience Publishing, New York. p 1-12.
Balagopalan, L., Chen, M.H., Geisbrecht, E.R., Abmayr, S.M. 2006. The CDM superfamily protein MBC directs myoblast fusion through a mechanism that requires phosphatidylinositol 3,4,5-triphosphate binding but is independent of direct interaction with DCrk. Mol. Cell. Biol. 26, 9442-9455. Abstract
Guelman, S., Suganuma, T., Florens, L., Weake, V.M., Swanson, S.K., Washburn, M.P., Abmayr, S.M., Workman, J.L. 2006. The essential gene wda encodes a WD40 repeat subunit of Drosophila SAGA required for histone H3 acetylation. Mol. Cell. Biol. 26, 7178-7189. Abstract
Guelman, S., Suganuma, T., Florens, L., Swanson, S.K., Kiesecker, C.L., Kusch, T., Anderson, S., Yates, J.R., Washburn, M.P., Abmayr, S.M., Workman, J.L. 2006. Host cell factor and an uncharacterized SANT domain protein are stable components of ATAC, a novel dAda2A/dGcn5-containing histone acetyltransferase complex in Drosophila. Mol. Cell. Biol. 26, 871-882. Abstract
Geisbrecht, E.R., Haralalka, S., Swanson, S.K., Florens, L., Washburn, M.P. Abmayr, S.M. 2008. Drosophila ELMO/CED-12 interacts with Myoblast city to direct myoblast fusion and ommatidial organization. Dev. Biol. 314, 137-149. Abstract
Weake, V.M., Lee, K.K., Guelman, S., Lin, C.H., Seidel, C., Abmayr, S.M., Workman, J.L. 2008. SAGA-mediated H2B deubiquitination controls the development of neuronal connectivity in the Drosophila visual system. EMBO J. 27, 394-405. Abstract
Kocherlakota, K.S., Wu, J.M., McDermott, J., Abmayr, S.M. 2008. Analysis of the Cell Adhesion Molecular Sticks-and-Stones Reveals Multiple Redundant Functional Domains, Protein-Interaction Motifs and Phosphorylated Tyrosines that direct Myoblast Fusion in Drosophila melanogaster. Genetics. 178, 1371-83. Abstract
Abmayr, S.M., Zhuang, S., Geisbrecht, E.R. 2008. Myoblast Fusion in Drosophila. Cell Fusion, Overviews and Methods. (E. Chen, Ed.) Humana Press. Abstract
Suganuma T., Gutierrez, J.L., Li, B., Florens, L., Swanson, S.K., Washburn, M. P., Abmayr, S.M., Workman, J.L. 2008. ATAC is a double histone acetyltransferase complex that stimulates nucleosome sliding. Nat Struct Mol Biol. 15, 364-72. Abstract
Lin C.H., Li B., Swanson S.K., Zhang Y., Florens L., Washburn M.P., Abmayr S.M., Workman J.L. 2008. Heterochromatin protein 1a stimulates histone H3 lysine 36 demethylation by the Drosophila KDM4A demethylase. Mol. Cell. 32:696-706. Abstract
Shelton C., Kocherlakota K.S., Zhuang S., Abmayr S.M. 2009. The immunoglobulin superfamily member Hbs functions redundantly with Sns in interactions between founder and fusion-competent myoblasts. Development. 136:1159-68. Abstract
Zhuang, S., Shao, H., Guo, F., Trimble, R., Pearce, E.K., Abmayr, S.M. 2009. SNS and Duf/Kirre, the Drosophila orthologs of Nephrin and Neph, direct adhesion, fusion and formation of a slit diaphragm-like structure in insect nephrocytes. Development. 136:2335-44. Abstract
Haralalka, S., Abmayr, S.M. 2010. Myoblast Fusion in Drosophila. Exp. Cell Res. 316:3007-13. Abstract
Weake, V. M. , Swanson, S.K., Mushegian, A., Florens, L., Washburn, M.P., Abmayr, S.M., Workman, J.L. 2010. A novel histone fold domain-containing protein that replaces TAF6 in Drosophila SAGA is required for SAGA-dependent gene expression. Genes Dev. 23:2818-23. Abstract
Suganuma, T., Mushegian, A., Swanson, S.K., Abmayr, S.M., Florens, L., Washburn, M.P., Workman, J.L. 2010. The ATAC acetyltransferase complex coordinates MAP kinases to regulate JNK target genes. Cell. 142:726-36. Abstract
Kwon, S.H., Florens, L., Swanson, S.K., Washburn, M.P., Abmayr, S.M., Workman, J.L. 2010. Heterochromatin protein 1 (HP1) connects the FACT histone chaperone complex to the phosphorylated CTD of RNA polymerase II. Genes Dev. 24:2133-45. Abstract
Haralalka, S., Shelton, C., Janzen, E., Abmayr, S.M. 2011 Asymmetric Mbc, active Rac1, and F-actin foci in the fusion-competent myoblasts direct myoblast fusion in Drosophila. Development. 138, 1551-1562. Abstract
Weake, V. M., Dyer, J.O., Seidel, C., Box, A., Swanson, S. K., Peak, A., Florens, L., Washburn, M.P., Abmayr, S.M., Workman, J.L. Post-transcription initiation function of the ubiquitous SAGA complex in tissue-specific gene activation. 2011. Genes Dev. 25: 1499-1509. Abstract
Kaipa B. R., Shao, H., Schäfer, G., Trinkewitz, T., Groth, V., Liu, J., Beck, L., Bogdan, S., Abmayr S.M., Önel, S.F. 2013. Dock mediates Scar- and WASp-dependent actin polymerization through interaction with cell adhesion molecules in founder cells and fusion-competent myoblasts. J. Cell Sci. 126: 360-72. Abstract
Lin, C-H., Paulson, A., Abmayr, S.M., Workman, J.L. 2012. HP1a Targets the Drosophila KDM4A Demethylase to a Subset of Heterochromatic Genes to Regulate H3K36me3 Levels. PLoS One 7: e39758. Abstract
Haralalka, S., Cartwright, H. N., Abmayr, S.M. 2012. Recent advances in imaging embryonic myoblast fusion in Drosophila. Methods 56: 55-62. Abstract
Abmayr, S.M., Pavlath, G. S. 2012. Myoblast Fusion: Lessons from flies and mice. Development 139, 641-656. Abstract
Mohan, R. D., Dialynis, G., Weake, V. M., Liu, J., Martin-Brown, S., Florens, L., Washburn, M. P., Workman, J. L., Abmayr, S.M. 2014. Loss of Drosophila Ataxin-7, a SAGA subunit, reduces H2B ubiquitination and leads to neural and retinal degeneration. Genes Dev. 28: 259-272. Abstract
Mohan, R. D., Abmayr, S. M., Workman, J.L. 2014. The expanding role for chromatin and transcription in polyglutamine disease. Curr. Opin. Gene. Dev. 26: 96–104. Abstract
Mohan, R. D., Abmayr, S. M., Workman, J. L. 2014. Pulling complexes out of complex diseases: Spinocerebellar Ataxia 7. Rare Dis. 2: e28859. Abstract
Haralalka, S., Shelton, C., Cartwright, H. N., Guo, F., Trimble, R., Kumar, R. P., Abmayr, S. M. 2014. Live imaging provides new insights on dynamic F-actin filopodia and differential endocytosis during myoblast fusion in Drosophila. PLoS One 9: e114126. Abstract
Kumar, R. P., Dobi, K., Baylies, M. B., Abmayr, S.M. 2015. The Drosophila T-box transcription factor Midline determines specific muscle identities. Genetics. 3:777-91. Abstract
Huang, F., Paulson, A., Dutta, A., Venkatesh, S., Smolle, M., Abmayr, S. M., Workman, J. L. 2014. Histone acetyltransferase Enok regulates oocyte polarization by promoting expression of the actin nucleation factor spire. Genes Dev. 28: 2750-2763. Abstract
Huang, F., Saraf, A., Florens, L., Kusch, T., Swanson, S. K., Szerszen, L. T., Li, G., Dutta, A., Washburn, M. P., Abmayr, S. M., Workman, J. L. 2016. Genes Dev. in press.
Huang, F., Abmayr, S. M., Workman, J. L. 2016. Regulation of KAT6 acetyltransferases and their roles in cell cycle progression, stem cell maintenance, and human disease. Mol. Cell. Biol. in press. Abstract
Dutta, A., Abmayr, S. M., Workman, J. L. 2016. Diverse Activities of Histone Acylations Connect Metabolism to Chromatin Function. Mol Cell. Abstract
Huang, F., Abmayr, S. M., Workman, J. L. 2016. Limiting PCNA-unloading at the G1/S transition. Cell Cycle. Abstract
Soffers, J. H., Li, X., Abmayr, S. M., Workman, J. L. 2016. Reading and Interpreting the Histone Acylation Code. Genomics Proteomics Bioinformatics. Abstract
Dutta, A., Sardiu, M., Gogol, M., Gilmore, J., Zhang, D., Florens, L., Abmayr, S. M., Washburn, M. P., Workman, J. L. 2017. Composition and Function of Mutant Swi/Snf Complexes. Cell Rep. Abstract
Dyer, J. O., Dutta, A. Gogol, M., Weake, V. M., Dialynas, G., Wu, X., Seidel, C., Zhang, Y., Florens, L., Washburn, M. P., Abmayr, S. M., Workman, J. L. 2017. Myeloid Leukemia Factor Acts in a Chaperone Complex to Regulate Transcription Factor Stability and Gene Expression. J Mol Biol. Abstract
Li, X., Seidel, C. W., Szerszen, L. T., Lange, J. J., Workman, J. L., Abmayr, S. M. 2017 Enzymatic modules of the SAGA chromatin-modifying complex play distinct roles in Drosophila gene expression and development. Genes Dev. Abstract