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Thomas Jefferson University - James B. Jaynes, Ph.D.
James B. Jaynes, Ph.D.

Biochemistry and Molecular Biology
Thomas Jefferson University
Jefferson Medical College
Department of Biochemistry and Molecular Biology
Associate Professor Appointed: 1992

Mailing Address
1020 Locust Street - Room JAH-490
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-4778
jaynes@jci.tju.edu
Qualifications
Seattle, University of Washington, B.S., Physics

Seattle, University of Washington, Ph.D., Biochemistry

Expertise and Research Interests
Changes in gene transcription are important in the progression of cancer, in most other human diseases, and in the aging process, as well as in the development of multicellular organisms at all stages. A detailed understanding of how such changes are regulated is the basis of both diagnostic tools and intervention strategies. Further advancement holds the promise of novel approaches, and of increased effectiveness of current approaches. Many questions remain about the fundamental processes involved. Tools available in Drosophila make it possible to study mechanisms of action and interaction in detail, in a true in vivo context.

In Drosophila, a cascade of nuclear regulatory events establishes very early differences in cell fates by producing intricate patterns of gene expression. Many of these pattern-forming genes encode DNA binding proteins that regulate each other's expression, and subsequently instruct the rest of the genome in a manner appropriate to each position in the organism. Recent work has shown that these regulatory proteins are conserved across the evolutionary distance separating flies and humans, both in terms of primary structure, implying similarity in mechanism, and in how the regulatory scheme in which they function solves the common problems of a developing multi-cellular organism. Therefore, a detailed understanding of the interactions of conserved regulators in one system has important implications for their homologs in other systems.

One focus of my laboratory is to understand regulatory principles by focusing on interactions of the homeodomain-containing transcription factor Engrailed. Engrailed is a potent repressor that recruits the corepressor Groucho, a homolog of the TLE family of mammalian cofactors. We are currently studying interactions between En and the conserved Pbx and Meis1 families of Hox protein cofactors, which act as oncogenes in mammals. This interaction confers a novel activity on the Meis1-Pbx complex (in Drosophila, Hth-Exd), that of transcriptional repression. Future studies will focus on the biochemical interactions among these factors, and on the functional consequences of altering those interactions.

My laboratory also studies mechanisms of chromatin-based gene regulation involving Polycomb-responsive elements and an insulator, recently discovered in a locus control region of the well-characterized Drosophila gene even-skipped. We address basic questions of how transcriptional memory and chromosome organization work in 3 dimensions in the nucleus. This will provide a clearer understanding of how proteins that carry out these functions recognize appropriate target sites in vivo, and the consequences of that recognition for the regulation of nearby genes. Understanding the mechanisms underlying these processes will provide novel ways to approach problems such as cancer, which is caused in part by misregulation of gene expression and chromatin structure.
Other Expertise
In a collaborative project with the Alex Mazo laboratory, we are studying the functions of the novel histone methyltransferase Trithorax-related (TRR). These studies reveal that this protein is a coactivator of the nuclear receptor complex of EcR-USP, acting in conjunction with ecdysone to up-regulate hedgehog gene expression during morphogenetic furrow progression in Drosophila eye development. This is the first H3-K4 methylase known to be directly involved in steroid hormone-regulated gene expression.
Industrial Relevance
Please see sections on expertise.
Keywords
Biochemistry; Biophysics; Cell Biology; Developmental Biology; Genetics; Human Physiology; Pharmacology; larva; fusion gene; drosophilidae; embryogenesis; gene mutation; stress protein; transgenic animal; transcription factor; nucleic acid sequence; developmental genetics; invertebrate embryology; genetic promoter element; gene induction repression; protein structure function
Publications
  • Miki Fujioka, Xian Wu, and James B. Jaynes. A chromatin insulator mediates transgene homing and very long-range enhancer-promoter communication (2009) Development 136: 3077-3087. http://dev.biologists.org/cgi/content/full/develop;136/18/3077

  • Fujioka, M., Yusibova, G.L., Zhou, J., and Jaynes, J.B. The DNA binding Polycomb-group protein Pleiohomeotic maintains both active and repressed transcriptional states through a single site. Development 135: 4131-4139. http://dev.biologists.org/cgi/content/full/135/24/4131

  • Farhan Khan*, Miki Fujioka*, Pinaki Datta*, Teresa Fernandes-Alnemri, James B. Jaynes, and Emad S. Alnemri. The interaction of DIAP1 with dOmi/HtrA2 regulates cell death in Drosophila; Cell Death and Differentiation 15: 1073-1083, 2008. *These authors contributed equally to the work. URL: http://www.nature.com/cdd/journal/v15/n6/abs/cdd200819a.html

  • Petruk, S., Sedkov, Y., Riley, K. M., Hodgson, J., Schweisguth, F., Hirose, S., Jaynes, J. B., Brock, H. W., and Mazo, A. Transcription of bxd non-coding RNAs promoted by Trithorax represses Ubx in cis by transcriptional interference; Cell 127: 1209-1221, 2006.

  • Fujioka*, M., Wessells*, R.J., Han, Z., Liu, J., Fitzgerald, K., Yusibova, G.L., Zamora, M., Ruiz-Lozano, P., Bodmer, R., and Jaynes, J.B. Embryonic even skipped-dependent muscle and heart cell fates are required for normal adult activity, heart function, and lifespan, Circ. Res. 2005;97: 1108-1114. *These authors contributed equally to the work. http://circres.ahajournals.org/cgi/content/full/01.RES.0000191546.08532.B2?ijkey=bYfjV61Jgd8UJzg&keytype=ref.

  • Jaynes, J.B., and Fujioka, M. Drawing lines in the sand: even skipped et al., and parasegment boundaries, Dev. Biol. 2004;269: 609-622. [erratum: Dev. Biol. 2004;272: 277-278.] http://www.sciencedirect.com/science/article/B6WDG-4C76GWX-2/2/f4e00f15570d5ad8539161582bba2527

  • Landgraf, M., Jeffrey, V., Fujioka, M., Jaynes, J.B., and Bate, M. Embryonic origins of a motor system: motor dendrites form a myotopic map in Drosophila, PLoS  Biology 2003;1: 221-230.

  • Sedkov, Y., Cho-Fertikh, E., Petruk, S., Smith, S.T., Cherbas, L., Jones, R.S., Canaani, E., Jaynes, J.B., and Mazo, A. Methylation at lysine 4 of histone H3 in ecdysone-dependent development of Drosophila, Nature 2003;426: 78-83.

  • Fujioka, M., Lear, B.C., Landgraf, M., Yusibova, G.L., Zhou, J., Riley, K.M., Patel, N.H., and Jaynes, J.B. Even-skipped, acting as a repressor, regulates axonal projections in Drosophila, Development 2003;130: 5385-5400.

  • McDonald, J.A., Fujioka, M., Jaynes, J.B., and Doe, C.Q. Specification of RP2 motoneuron fate: integration of positive and negative transcription factor inputs by a minimal eve enhancer, J. Neurobiol. 2003;57: 193-203.

  • Kobayashi, M, Fujioka, M, Tolkunova, EN, Deka, D, Abu-Shaar, M, Mann, RS, and Jaynes, JB. Engrailed cooperates with extradenticle and homothorax to repress target genes in Drosophila. Development 2003;130:741-751.

  • Srinivasula, SM, Datta, P, Kobayashi, M, Wu, JW, Fujioka, M, Hegde, R, Zhang, Z, Mukattash, R, Fernandes-Alnemri, T, Shi, Y, Jaynes, JB, and Alnemri, ES. sickle, a novel Drosophila death gene in the reaper/hid/grim region, encodes an IAP-inhibitory protein. Curr. Biol. 2002;12:125-130.

  • Han*, Z, Fujioka*, M, Su, M, Liu, M, Jaynes, JB, and Bodmer, R. Transcriptional integration of competence modulated by mutual repression generates cell-type specificity within the cardiogenic mesoderm. Dev. Biol. 2002;252:225-240. *These authors contributed equally to the work.

  • Fujioka, M, Yusibova, GL, Patel, NH, Brown, SJ, and Jaynes, JB. The repressor activity of Even-skipped is highly conserved, and is sufficient to activate engrailed and to regulate both the spacing and stability of parasegment boundaries. Development 2002;129:4411-4421.

  • Americo, J, Whiteley, M, Brown, JL, Fujioka, M, Jaynes, JB, and Kassis, JA. A complex array of DNA-binding proteins required for pairing-sensitive silencing by a polycomb group response element from the Drosophila engrailed gene. Genetics 2002;160:1561-1571.

  • Zhu, W, Foehr, M, Jaynes, JB, and Hanes, SD. Drosophila SAP18, a member of the Sin3/Rpd3 histone deacetylase complex, interacts with Bicoid and inhibits its activity. Dev. Genes Evol. 2001;211:109-117.

  • Park, Y, Fujioka, M, Kobayashi, M, Jaynes, JB, and Datta, S. even skipped is required to produce a trans-acting signal for larval neuroblast proliferation that can be mimicked by ecdysone. Development 2001;128:1899-1909.

  • Kobayashi, M, Goldstein, RE, Fujioka, M, Paroush, Z, and Jaynes, JB. Groucho augments the repression of multiple Even-skipped target genes in establishing parasegment boundaries. Development 2001;128:1805-1815.

  • Fujioka, M, Emi-Sarker, Y, Yusibova, GL, Goto, T, and Jaynes, JB. Analysis of an even-skipped rescue transgene reveals both composite and discrete neuronal and early blastoderm enhancers, and multi-stripe positioning by gap gene repressor gradients. Development 1999;126:2527-2538.

  • Baines, RA, Robinson, SG, Fujioka, M, Jaynes, JB, and Bate, M. Postsynaptic expression of tetanus toxin light chain blocks synaptogenesis in Drosophila. Curr. Biol. 1999;9:1267-1270.

  • Tolkunova, EN, Fujioka, M, Kobayashi, M, Deka, D, and Jaynes, JB. Two distinct types of repression domain in Engrailed: one interacts with the Groucho corepressor and is preferentially active on integrated target genes. Mol. Cell. Biol. 1998;18:2804-2814.

  • Park, Y, Fujioka, M, Jaynes, JB, and Datta, S. Drosophila homeobox gene eve enhances trol, an activator of neuroblast proliferation in the larval CNS. Dev. Genet. 1998;23:247-257.

  • Smith, ST and Jaynes, JB. A conserved region of engrailed, shared among all en-, gsc-, Nk1-, Nk2- and msh-class homeoproteins, mediates active transcriptional repression in vivo. Development 1996;122:3141-3150.

  • John, A, Smith, ST, and Jaynes, JB. Inserting the Ftz homeodomain into Engrailed creates a dominant transcriptional repressor that specifically turns off Ftz target genes in vivo. Development 1995;121:1801-1813.

  • Fujioka, M, Jaynes, JB, and Goto, T. Early even-skipped stripes act as morphogenetic gradients at the single cell level to establish engrailed expression. Development 1995;121:4371-4382.

  • Jaynes, JB and O'Farrell, PH. Active repression of transcription by the Engrailed homeodomain protein. EMBO J. 1991;10:1427-1433.

  • Jaynes, JB and O'Farrell, PH. Activation and repression of transcription by homoeodomain-containing proteins that bind a common site. Nature 1988;336:744-749.

  • Jaynes, JB, Johnson, JE, Buskin, JN, Gartside, CL, and Hauschka, SD. The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer. Mol. Cell. Biol. 1988;8:62-70.

Individual Expertise profile of James B. Jaynes, Ph.D., Copyright © James B. Jaynes, Ph.D..
Last Updated by James Jaynes, Ph.D. : Thursday, August 27, 2009 12:03:01 PM



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