Reid C. Johnson, Ph.D.

Laboratory Address:
Department of Biological Chemistry
David Geffen School of Medicine at UCLA
BSRB 357A
Los Angeles, CA 90095

Work Address:
351B BSRB
CAMPUS - 173717
CA Department of Biological Chemistry
David Geffen School of Medicine at UCLA
BSRB 351B
Los Angeles, CA 90095

Affiliations
Affiliations
Professor, Biological Chemistry
Member, Biochemistry, Biophysics & Structural Biology GPB Home Area, Gene Regulation GPB Home Area, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, JCCC Gene Regulation Program Area, Molecular Biology Institute
Research Interests
(1) One of the ways Salmonella, a major cause of gastroenteritis or food poisoning, evades the immune system is to change flagellar proteins, which are major cell surface antigens. Inversion of a 1 kb segment of the chromosome by the Hin recombinase regulates flagellar synthesis by switching the orientation of a transcriptional promoter. Our work has shown that Hin dimers bound to specific DNA sites flanking the inverting segment, together with regulatory proteins called Fis bound to an enhancer-like DNA segment, assemble into an ?invertasome? complex with the help of the DNA bending protein HU. DNA cutting, translocation of DNA strands, and ligation all occur within this nucleoprotein machine. We are trying to determine the molecular structure of the invertasome and the conformational changes that accompany the different reaction steps. The lab uses a variety of approaches including genetics, site-directed crosslinking, fluorescence resonance energy transfer, electron microscopy, X-ray crystallography, and molecular modeling to probe these steps. (2) Fis is one of the most abundant DNA binding proteins in rapidly growing cells, though its levels vary enormously with growth conditions. We are also studying its role as a regulator of transcription and chromosome structure. Fis selectively activates and silences transcription of specific genes, and we hope to learn how Fis couples cell physiology to global gene expression patterns. Mechanistic aspects of transcriptional activation by Fis are being defined using genetic and biochemical methods, and x-ray crystallography. We are pursuing recent data suggesting Fis performs an active role in packaging the chromosome into the nucleoid. (3) HMGB proteins are abundant constituents of eukaryotic chromatin. They deform DNA structure and collaborate with other transcription factors to co-regulate expression of a subset of genes. Our previous work has emphasized the structural and functional DNA binding properties of mammalian HMGB1 and yeast Nhp6A/B. We are using yeast as a model system to further study the various roles of HMGB proteins in modulating chromatin structure and function. Current work is focused on identifying yeast genes whose expression is co-regulated by Nhp6A/B and investigating how Nhp6A/B influence their transcription.
Biography

Reid C. Johnson is a Professor of Biological Chemistry in the UCLA School of Medicine, where he joined the faculty in 1986. He received his Ph.D. from the University of Wisconsin-Madison in 1983 and did postdoctoral work at Caltech. Dr. Johnson has had a long standing research interest in mechanisms and control of specialized DNA recombination reactions, such as transposition and site-specific recombination. An additional focus of his laboratory has concerned the varied functions of abundant nucleoid-associated DNA bending proteins in regulating transcription reactions and chromosome behavior in microorganisms. This work has recently been extended to include HMGB chromatin-associated proteins in eukaryotic cells, especially yeast.

Publications

A selected list of publications:

McLean MM, Chang Y, Dhar G, Heiss JK, Johnson RC.   Multiple interfaces between a serine recombinase and an enhancer control site-specific DNA inversion eLife, 2013; 2: e01211.
Hancock Stephen P, Ghane Tahereh, Cascio Duilio, Rohs Remo, Di Felice Rosa, Johnson Reid C   Control of DNA minor groove width and Fis protein binding by the purine 2-amino group Nucleic Acids Research, 2013; 41(13): 6750-6760.
Mandali Sridhar, Dhar Gautam, Avliyakulov Nuraly K, Haykinson Michael J, Johnson Reid C   The site-specific integration reaction of Listeria phage A118 integrase, a serine recombinase Mobile DNA, 2013; 4(1): 2.
Nafissi Maryam, Chau Jeannette, Xu Jimin, Johnson Reid C   Robust translation of the nucleoid protein Fis requires a remote upstream AU element and is enhanced by RNA secondary structure Journal of Bacteriology, 2012; 194(10): 2458-2469.
Yazdi, N.H., Guet, C.C., Johnson, R.C., Marko, J.F.   Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions Mol. Microbiol, 2012; 86: 1318-1333.
Graham John S, Johnson Reid C, Marko John F   Concentration-dependent exchange accelerates turnover of proteins bound to double-stranded DNA Nucleic Acids Research, 2011; 39(6): 2249-2259.
Graham John S, Johnson Reid C, Marko John F   Counting proteins bound to a single DNA molecule Biochemical and biophysical research communications, 2011; 415(1): 131-134.
Xiao Botao, Zhang Houyin, Johnson Reid C, Marko John F   Force-driven unbinding of proteins HU and Fis from DNA quantified using a thermodynamic Maxwell relation Nucleic Acids Research, 2011; 39(13): 5568-5577.
Heiss John K, Sanders Erin R, Johnson Reid C   Intrasubunit and Intersubunit Interactions Controlling Assembly of Active Synaptic Complexes during Hin-Catalyzed DNA Recombination Journal of Molecular Biology, 2011; 411(4): 744-764.
Johnson Reid C, McLean Meghan M   Recombining DNA by protein swivels Structure , 2011; 19(6): 751-753.
Dowell, NL, Sperling, AS, Mason, MJ, and Johnson, RC   Chromatin-dependent binding of the S. cerevisiae HMGB protein Nhp6A affects nucleosome dynamics and transcription Genes & Development, 2010; 24: 2031-2042.
Dowell Noah L, Sperling Adam S, Mason Michael J, Johnson Reid C   Chromatin-dependent binding of the S. cerevisiae HMGB protein Nhp6A affects nucleosome dynamics and transcription Genes & development, 2010; 24(18): 2031-42.
Xiao, B, Johnson, RC, and Marko, JF   Modulation of HU-DNA interactions by salt concentration and applied force Nucleic Acids Res, 2010; 38: 6176-6185.
Stella, S, Cascio, D, and Johnson RC   The shape of the DNA minor groove directs binding by the DNA-bending protein Fis Genes & Development, 2010; 24(8): 814-826.
Dhar G, Heiss JK, and Johnson RC   Mechanical constraints on Hin subunit rotation imposed by the Fis-enhancer system and DNA supercoiling during site-specific recombination Molecular Cell , 2009; 34: 746-759.
Dhar Gautam, Heiss John K, Johnson Reid C   Mechanical constraints on Hin subunit rotation imposed by the Fis/enhancer system and DNA supercoiling during site-specific recombination Molecular cell, 2009; 34(6): 746-59.
Dhar G, McLean MM, Heiss JK, and Johnson RC   The Hin recombinase assembles a tetrameric protein swivel that exchanges DNA strands Nucleic Acids Res, 2009; 37: 746-759.
Dhar Gautam, McLean Meghan M, Heiss John K, Johnson Reid C   The Hin recombinase assembles a tetrameric protein swivel that exchanges DNA strands Nucleic acids research, 2009; 37(14): 4743-56.
Johnson RC, and Heiss JK   Assembly of a tightly interwound DNA recombination complex poised for deletion Structure, 2008; 16: 653-655.
Johnson RC, Stella S, Heiss JK   Bending and compaction of DNA by proteins, In: Protein-Nucleic Acid Interactions, eds: PA Rice and CC Correll (RSC Press, Cambridge, UK), 2008; pp. 176-220.
Papagiannis CV, Sam MD, Abbani MA, Cascio D, Clubb, RT, and Johnson, RC   Fis targets assembly of the Xis nucleoprotein filament to promote excisive recombination by phage lambda J. Mol. Biol, 2007; 367: 328-343.
Abbani MA, Papagiannis CV, Sam MD, Cascio D, Johnson RC and Clubb RT   Structure of the cooperative Xis-DNA complex reveals a micronucleoprotein filament that regulates phage lambda intasome assembly Proc. Natl. Acad. Sci. USA, 2007; 104: 2109-2114.
Typas A, Stella S, Johnson RC, and Hengge R   The -35 sequence and the Fis-sigma factor interface determine sigma S selectivity of the proP (P2) promoter in Escherichia coli Mol. Microbiol, 2007; 63: 780-796.
Hanover, J.A. Love, D.C. DeAngelis, N. O'Kane, M.E. Lima-Miranda, R. Schulz, T. Yen, Y-M. Johnson, R.C. Prinz, W.A.   The high mobility group box transcription factor NHP6Ap enters the nucleus by a calmodulin-dependent, Ran-independent pathway J. Biol. Chem, 2007; 282: 33,742-33,751.
Skoko D, Yoo D, Bai H, Schnurr B, Yan J, McLeod SM, Marko JF, and Johnson RC   Mechanism of chromosome compaction and looping by the Escherichia coli nucleoid protein Fis J. Mol. Biol, 2006; 364: 777-798.
Dai Y, Wong B, Yen YM, Oettinger MA, Kwon J, and Johnson RC   Determinants of HMGB proteins required to promote RAG1/2-recombination signal sequence complex assembly and catalysis during V(D)J recombination Molecular and Cellular Biology. , 2005; 25(11): 4413-4425.
Skoko D, Yan J, Johnson RC, and Marko JF   Low-force DNA condensation and discontinuous high-force decondensation reveal a loop-stabilizing function of the protein Fis Phys. Rev. Lett, 2005; 95: 208101.
Dhar G, Sanders ER, and Johnson RC   Architecture of the Hin synaptic complex during recombination: the recombinase subunits translocate with the DNA strands Cell. , 2004; 119: 33-45.
Sam MD, Cascio D, Johnson RC, and Clubb RT   Crystal structure of the excisionase-DNA complex from bacteriophage lambda Journal of Molecular Biology. , 2004; 338: 229-240.
Skoko D, Wong B, Johnson RC, and Marko JF   Micromechanical analysis of the binding of DNA-bending proteins HMGB1, NHP6A, and HU reveals their ability to form highly stable DNA-protein complexes Biochemistry. , 2004; 43: 13867-13874.
Sanders ER and Johnson RC   Stepwise dissection of the Hin-catalyzed recombination reaction from synapsis to resolution Journal of Molecular Biology. , 2004; 340: 753-766.
Merickel SK and Johnson RC   Topological analysis of Hin-catalyzed DNA recombination in vivo and in vitro Mol. Microbiol, 2004; 51: 1143-1154.
Aiyar SE, McLeod SM, Ross W, Hirvonen CA, Thomas MS, Johnson RC, and Gourse RL   Architecture of Fis-activated transcription complexes at the Escherichia coli rrnB P1 and rrnE P1 promoters Journal of Molecular Biology. , 2002; 316: 501-516.
Wong B, Masse JE, Yen Y-M, Feigon J and Johnson RC   Binding to cisplatin-modified DNA by the S. cerevisiae HMGB protein NHP6A Biochemistry, 2002; 41: 5404-5414.
Sam MD, Papagiannis CV, Connolly KM, Corselli L, Iwahara J, Lee J, Phillips M, Wojciak JM, Johnson RC, and Clubb RT   Regulation of directionality in bacteriophage lambda site-specific recombination: structure of the Xis protein Journal of Molecular Biology, 2002; 324: 791-805.
Merickel SK, Sanders ER, Vzquez-Ibar JL, and Johnson RC   Subunit exchange and the role of dimer flexibility in DNA binding by the Fis protein Biochemistry , 2002; 41: 5788-5798.
Chiu TK, Sohn C, Dickerson RE, and Johnson RC   Testing water-mediated DNA recognition by the Hin recombinase EMBO J, 2002; 21: 801-814.
McLeod SM, Aiyar SE, Gourse RL & Johnson RC   The C-terminal domains of the RNA polymerase alpha subunits: Contact site with Fis and localization during co-activation with CRP at the Escherichia coli proP P2 promoter J. Mol. Biol. , 2002; 316: 517-529.
Mitsouras K, Wong B, Arayata C, Johnson RC, and Carey M   The DNA architectural protein HMGB1 displays two distinct modes of action that promote enhanceosome assembly Molecular and Cellular Biology. , 2002; 22: 4390-4401.
Masse JE, Wong B, Yen Y-M, Allain FHT, Johnson RC and Feigon J   The S. cerevisiae DNA architectural HMGB protein NHP6A complexed with DNA: DNA and protein conformational changes upon binding J. Mol. Biol. , 2002; 323: 263-284.
McLeod SM and Johnson RC   Control of transcription by nucleoid-associated proteins Current Opinion in Microbiology, 2001; 4: 152-159.
Yen YM, Roberts PM and Johnson RC   Nuclear localization of the S. cerevisiae HMG protein NHP6A occurs by a Ran-independent non-classical pathway Traffic, 2001; 2: 449-464.
McLeod SM, Xu J and Johnson RC   Co-activation of the RpoS-dependent proP P2 promoter by Fis and CRP J. Bacteriol, 2000; 182: 4180-4187.
Ellwood KB, Yen YM, Johnson RC, and Carey M   Mechanism for specificity by HMG-1 in enhanceosome assembly Molecular and Cellular Biology. , 2000; 20: 4359-4370.
Cheng YS, Yang WZ, Johnson RC, and Yuan HS   Structural analysis of the transcriptional activation on Fis: crystal structures of six Fis mutants with different activation properties Journal of Molecular Biology. , 2000; 302: 1139-1151.
McLeod SM, Xu J, Crampton SE, Gaal T, Gourse RL and Johnson RC   Localization of amino acids required for Fis to function as a class II transcriptional activator at the RpoS-dependent proP P2 promoter J. Mol. Biol, 1999; 294: 333-346.
Ellwood K, Huang W, Johnson RC and Carey M   Multiple layers of cooperativity regulate enhancesome-responsive RNA polymerase II transcription complex assembly Mol. Cell. Biol, 1999; 19: 2613-2623.
Allain FH, Yen YM, Masse JE, Schultze P, Dieckmann T, Johnson RC, Feigon J   Solution structure of the HMG protein NHP6A and its interaction with DNA reveals the structural determinants for non-sequence-specific binding The EMBO J. , 1999; 18: 2563-2579.
Landis L, Xu J, and Johnson RC,   The cAMP receptor protein CRP can function as an osmoregulator of transcription in Escherichia coli Genes & Development. , 1999; 13: 3081-3091.
Merickel SK, Haykinson MJ, and Johnson RC   Communication between Hin recombinase and Fis regulatory subunits during coordinate activation of Hin-catalyzed site-specific DNA inversion Genes & Development , 1998; 12: 2803-2816.
Yang WZ, Ko TP, Corselli L, Johnson RC and Yuan HS   Conversion of a beta-strand to an alpha-helix induced by a single-site mutation identified in the crystal structure of Fis mutant Pro26Ala, Protein Science, 1998; 7: 1875-1883.
Yen YM, Wong B, and Johnson RC   Determinants of DNA binding and bending by the Saccharomyces cerevisiae high mobility group protein NHP6A that are important for its biological activities. Role of the unique N terminus and putative intercalating methionine The Journal of Biological Chemistry. , 1998; 273: 4424-4435.
Xu J and Johnson RC   Activation of RpoS-dependent proP P2 transcription by the Fis protein in vitro Journal of Molecular Biology. , 1997; 270: 346-359.
Safo MK, Yang WZ, Corselli L, Cramton SE, Yuan HS, and Johnson RC   The transactivation region of the Fis protein that controls site-specific DNA inversion contains extended mobile beta-hairpin arms The EMBO J. , 1997; 16: 6860-6873.
Haykinson MJ, Johnson LM, Soong J, and Johnson RC   The Hin dimer interface is critical for Fis-mediated activation of the catalytic steps of site-specific DNA inversion Current Biology , 1996; 6: 163-177.
Pan CQ, Finkel SE, Cramton SE, Feng JA, Sigman DS, and Johnson RC   Variable structures of Fis-DNA complexes determined by flanking DNA-protein contacts Journal of Molecular Biology. , 1996; 264: 675-695.
Paull TT, Carey M and Johnson RC   Yeast HMG proteins NHP6A/B potentiate promoter-specific transcriptional activation in vivo and assembly of pre-initiation complexes in vitro Genes and Development, 1996; 10: 2769-2781.
Giuntoli Rebecca D, Linzer Nora B, Banigan Edward J, Sing Charles E, de la Cruz Monica Olvera, Graham John S, Johnson Reid C, Marko John F   DNA-Segment-Facilitated Dissociation of Fis and NHP6A from DNA Detected via Single-Molecule Mechanical Response Journal of molecular biology, 2015; 427(19): 3123-36.
Hadizadeh Nastaran, Johnson Reid C, Marko John F   Facilitated Dissociation of a Nucleoid Protein from the Bacterial Chromosome Journal of bacteriology, 2016; 198(12): 1735-42.
Chang Yong, Johnson Reid C   Controlling tetramer formation, subunit rotation and DNA ligation during Hin-catalyzed DNA inversion Nucleic acids research, 2015; 43(13): 6459-72.
Xiao Botao, McLean Meghan M, Lei Xianbin, Marko John F, Johnson Reid C   Controlled rotation mechanism of DNA strand exchange by the Hin serine recombinase Scientific reports, 2016; 6(12): 23697.
Johnson Reid C   Site-specific DNA Inversion by Serine Recombinases Microbiology spectrum, 2015; 3(3): 1-36.
Hancock Stephen P, Stella Stefano, Cascio Duilio, Johnson Reid C   DNA Sequence Determinants Controlling Affinity, Stability and Shape of DNA Complexes Bound by the Nucleoid Protein Fis PloS one, 2016; 11(3): e0150189.