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Thomas Jefferson University - James B. Jaynes, PhD
James B. Jaynes, PhD

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

Mailing Address
1020 Locust Street - Room JAH-479
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-4778
james.jaynes@jefferson.edu
Qualifications
Seattle, University of Washington, B.S., Physics

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

Expertise and Research Interests
Embryos regulate their growth and development in many ways, but control of gene transcription is essential for directing cells along particular developmental pathways. 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 others expression, and subsequently instruct the rest of the genome in a manner appropriate to each position in the organism. These regulatory proteins are conserved across the evolutionary distance separating flies and humans. This applies to both their primary structure, implying similarity in mechanism, and often their developmental function. That is, the regulatory scheme in which they function solves a common problem of developing multi-cellular organisms. Our current studies revolve around understanding specific mechanisms of two types: first, which gene products interact directly with which genes and other gene products, and second, how this impinges on transcriptional regulation and, relatedly, the stability of the epigenome.

My laboratory focuses on the regulation and function of two homeodomain-containing proteins. The homeodomain is a highly conserved sequence-specific DNA binding domain found in transcriptional regulators from yeast to humans. One of these, Engrailed (En), is a potent repressor of transcription that recruits the corepressor Groucho, a homolog of the TLE family of mammalian cofactors. We are currently studying interactions between En and the Pbx and Meis/PREP families of Hox protein cofactors, which serve to increase its DNA-binding specificity and thereby direct it to particular target genes. The interaction with En confers a novel activity on the Meis/PREP-Pbx complex (in Drosophila, Hth-Exd), that of transcriptional repression. Our analysis focuses on the biochemical interactions among these factors, and on the functional consequences of altering those interactions.

Even-skipped (Eve) is another transcription factor that regulates developmental processes in a highly conserved fashion. Eve, like En, uses both Groucho-dependent and independent mechanisms to repress transcription. With the even-skipped gene (eve), we have the ability to completely rescue null mutants with a transgene, allowing us to functionally replace the endogenous gene. This facilitates our studies of its regulation in vivo. Currently, we are analyzing how long-range repression and activation occur over an entire genetic locus, through the regulation of chromatin structure. Included in the long-range regulatory elements of eve are a boundary region that helps to functionally isolate it from neighboring genes, and to maintain both the activated and repressed state within different developing lineages of cells. These activities are mediated by an insulator and a Polycomb-group response element. Both of these kinds of elements function in a variety of genes, and in mammals as well as in Drosophila, to regulate developmental processes like stem cell maintenance and differentiation. Understanding the underlying mechanisms will provide novel ways to attack problems like cancer, which is caused in part by mis-regulation 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; Cell Biology; Developmental Biology; Genetics; Human Physiology; Drosophila; drosophilidae; embryogenesis; gene regulation; transgenic animal; transcription factor; developmental genetics; invertebrate embryology; genetic promoter element; transcriptional regulation; chromatin; epigenetics; gene induction; gene repression; insulator; Polycomb group; maintenance element; protein structure function
Publications
  • Fujioka M., Sun G., Jaynes J.B. (2013) The Drosophila eve Insulator Homie Promotes eve Expression and Protects the Adjacent Gene from Repression by Polycomb Spreading. PLoS Genet 9(10): e1003883. doi:10.1371/journal.pgen.1003883.
  • http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003883
  • Fujioka, M., Gebelein, B., Cofer, Z.C., Mann, R.S., and Jaynes, J.B. Engrailed cooperates directly with Extradenticle and Homothorax on a distinct class of homeodomain binding sites to repress sloppy paired. Dev. Biol. 366, 382-392, 2012. http://dx.doi.org/10.1016/j.ydbio.2012.04.004
  • Fujioka, M. and Jaynes, J.B. Regulation of a duplicated locus: Drosophila sloppy paired is replete with functionally overlapping enhancers. Dev. Biol. 362, 309319, 2012. http://dx.doi.org/10.1016/j.ydbio.2011.12.001
  • Danika M. Johnston*, Yurii Sedkov*, Svetlana Petruk, Kristen M. Riley, Miki Fujioka, James B. Jaynes and Alexander Mazo (2011). Ecdysone- and NO-mediated gene regulation by competing EcR/Usp and E75A nuclear receptors during Drosophila development; Mol. Cell 44: 51-61. http://www.sciencedirect.com/science/article/pii/S1097276511006848
  • Miki Fujioka, Xian Wu, and James B. Jaynes. A chromatin insulator mediates transgene homing and very long-range enhancer-promoter communication. Development 136: 3077-3087, 2009. 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, 2008. 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, PhD, Copyright © James B. Jaynes, PhD.
Last Updated by James Jaynes, PhD : Wednesday, January 30, 2013 3:44:15 PM



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