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Jennifer A. Armstrong

Associate Dean of Faculty, Scripps College
Professor of Biology

Email: jarmstrong@kecksci.claremont.edu
Office: Balch 134
Phone: 909-607-9716
Office Hours: Mondays and Thursdays 8:30-9:30 and by appointment
Web Site: https://faculty.jsd.claremont.edu/jarmstrong

Educational Background
Postdoc, University of California, Santa Cruz
Ph.D., University of California, San Diego
B.S., New Mexico State University

Courses Taught

  • Genetics
  • Cell Biology
  • Introductory Biology (BIOL43L)
  • Molecular Biology Seminar/Laboratory
  • Epigenetics
  • Scripps Core I: Histories of the Present: Human Nature and Human Difference
  • Core II: Constructions of (Dis)Ability

Research Interests
chromatin and chromosome structure and gene regulation

Thesis Topics

My laboratory focuses on chromatin remodeling factors, which utilize the energy of ATP to slide, remodel, or assemble nucleosomes. Understanding the normal function of these proteins is critical since their loss can lead to mis-regulation of the genome and several distinct forms of disease, including cancer.

Selected Publications

  1. Kim S, Bugga L, Hong ES, Zabinsky R, Edwards RG, Deodhar PA, Armstrong JA. (2015). An RNAi-Based Candidate Screen for Modifiers of the CHD1 Chromatin Remodeler and Assembly Factor in Drosophila melanogaster. G3 6: 245-54.
    Abstract – The conserved chromatin remodeling and assembly factor CHD1 (chromodomains, helicase, DNA-binding domain) is present at active genes where it participates in histone turnover and recycling during transcription. In order to gain a more complete understanding of the mechanism of action of CHD1 during development, we created a novel genetic assay in Drosophila melanogaster to evaluate potential functional interactions between CHD1 and other chromatin factors. We found that overexpression of CHD1 results in defects in wing development and utilized this fully penetrant and reliable phenotype to conduct a small-scale RNAi-based candidate screen to identify genes that functionally interact with chd1 in vivo. Our results indicate that CHD1 may act in opposition to other remodeling factors, including INO80, and that the recruitment of CHD1 to active genes by RTF1 is conserved in flies.
    [Article – URL not found]
  2. Bugga L, McDaniel IE, Engie L, Armstrong JA. (2013). The Drosophila melanogaster CHD1 chromatin remodeling factor modulates global chromosome structure and counteracts HP1a and H3K9me2. PLoS One 8: e59496.
    Abstract – CHD1 is a conserved chromatin remodeling factor that localizes to active genes and functions in nucleosome assembly and positioning as well as histone turnover. Mouse CHD1 is required for the maintenance of stem cell pluripotency while human CHD1 may function as a tumor suppressor. To investigate the action of CHD1 on higher order chromatin structure in differentiated cells, we examined the consequences of loss of CHD1 and over-expression of CHD1 on polytene chromosomes from salivary glands of third instar Drosophila melanogaster larvae. We observed that chromosome structure is sensitive to the amount of this remodeler. Loss of CHD1 resulted in alterations of chromosome structure and an increase in the heterochromatin protein HP1a, while over-expression of CHD1 disrupted higher order chromatin structure and caused a decrease in levels of HP1a. Over-expression of an ATPase inactive form of CHD1 did not result in severe chromosomal defects, suggesting that the ATPase activity is required for this in vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.
    Article – https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059496
  3. Marta Radman-Livaja, Tiffani K. Quan, Lourdes Valenzuela, Jennifer A. Armstrong, Tibor van Welsem, TaeSoo Kim, Laura J. Lee, Stephen Buratowski, Fred van Leeuwen, Oliver J. Rando, Grant A. Hartzog. (2012). A Key Role for Chd1 in Histone H3 Dynamics at the 3′ Ends of Long Genes in Yeast. PLoS Genetics: 10.1371/journal.pgen.1002811.
    Abstract – Chd proteins are ATP–dependent chromatin remodeling enzymes implicated in biological functions from transcriptional elongation to control of pluripotency. Previous studies of the Chd1 subclass of these proteins have implicated them in diverse roles in gene expression including functions during initiation, elongation, and termination. Furthermore, some evidence has suggested a role for Chd1 in replication-independent histone exchange or assembly. Here, we examine roles of Chd1 in replication-independent dynamics of histone H3 in both Drosophila and yeast. We find evidence of a role for Chd1 in H3 dynamics in both organisms. Using genome-wide ChIP-on-chip analysis, we find that Chd1 influences histone turnover at the 5′ and 3′ ends of genes, accelerating H3 replacement at the 5′ ends of genes while protecting the 3′ ends of genes from excessive H3 turnover. Although consistent with a direct role for Chd1 in exchange, these results may indicate that Chd1 stabilizes nucleosomes perturbed by transcription. Curiously, we observe a strong effect of gene length on Chd1’s effects on H3 turnover. Finally, we show that Chd1 also affects histone modification patterns over genes, likely as a consequence of its effects on histone replacement. Taken together, our results emphasize a role for Chd1 in histone replacement in both budding yeast and Drosophila melanogaster, and surprisingly they show that the major effects of Chd1 on turnover occur at the 3′ ends of genes.
    Article – https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002811
  4. McDaniel IE, Lee JM, Berger MS, Hanagami CK, Armstrong JA. (2008). Investigations of CHD1 function in transcription and development of Drosophila melanogaster. Genetics 1: 583-587.
    Abstract – In this report we describe chd1 mutant alleles and show that the CHD1 chromatin-remodeling factor is important for wing development and fertility. While CHD1 colocalizes with elongating RNA polymerase II (Pol II) on polytene chromosomes, elongating Pol II can persist on chromatin in the absence of CHD1. These results clarify the roles of chromatin remodelers in transcription and provide novel insights into CHD1 function.
    Article: https://www.genetics.org/content/178/1/583.full
  5. Burgio G, La Rocca G, Sala A, Arancio W, Di Gesù D, Collesano M, Sperling AS, Armstrong JA, van Heeringen SJ, Logie C, Tamkun JW, Corona DF. 2008. Genetic identification of a network of factors that functionally interact with the nucleosome remodeling ATPase ISWI. PLoS Genetics 4: e1000089.
    Abstract – Nucleosome remodeling and covalent modifications of histones play fundamental roles in chromatin structure and function. However, much remains to be learned about how the action of ATP-dependent chromatin remodeling factors and histone-modifying enzymes is coordinated to modulate chromatin organization and transcription. The evolutionarily conserved ATP-dependent chromatin-remodeling factor ISWI plays essential roles in chromosome organization, DNA replication, and transcription regulation. To gain insight into regulation and mechanism of action of ISWI, we conducted an unbiased genetic screen to identify factors with which it interacts in vivo. We found that ISWI interacts with a network of factors that escaped detection in previous biochemical analyses, including the Sin3A gene. The Sin3A protein and the histone deacetylase Rpd3 are part of a conserved histone deacetylase complex involved in transcriptional repression. ISWI and the Sin3A/Rpd3 complex co-localize at specific chromosome domains. Loss of ISWI activity causes a reduction in the binding of the Sin3A/Rpd3 complex to chromatin. Biochemical analysis showed that the ISWI physically interacts with the histone deacetylase activity of the Sin3A/Rpd3 complex. Consistent with these findings, the acetylation of histone H4 is altered when ISWI activity is perturbed in vivo. These findings suggest that ISWI associates with the Sin3A/Rpd3 complex to support its function in vivo.
    Article – https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000089
  6. Armstrong JA. (2007). Negotiating the nucleosome: factors that allow RNA polymerase II to elongate through chromatin. Biochemistry and Cell Biology 85: 426-434.
    Abstract – Initiation by RNA polymerase II (Pol II) involves a host of enzymes, and the process of elongation appears similarly complex. Transcriptional elongation through chromatin requires the coordinated efforts of Pol II and its associated transcription factors: C-terminal domain kinases, elongation complexes, chromatin-modifying enzymes, chromatin remodeling factors, histone chaperones (nucleosome assembly factors), and histone variants. This review examines the following: (i) the consequences of the encounter between elongating Pol II and a nucleosome, and (ii) chromatin remodeling factors and nucleosome assembly factors that have recently been identified as important for the elongation stage of transcription.
    Article – https://pubmed.ncbi.nlm.nih.gov/17713578/
  7. Armstrong, JA and Schulz, JS. (2007). Agarose Gel Electrophoresis. Current Protocols in Essential Laboratory Techniques.  Wiley Publishers
  8. Corona DF, Siriaco G, Armstrong JA, Snarskaya N, McClymont SA, Scott MP, Tamkun JW. (2007). ISWI regulates higher-order chromatin structure and histone H1 assembly in vivo. PLoS Biology  5: e232.
    Abstract – Imitation SWI (ISWI) and other ATP-dependent chromatin-remodeling factors play key roles in transcription and other processes by altering the structure and positioning of nucleosomes. Recent studies have also implicated ISWI in the regulation of higher-order chromatin structure, but its role in this process remains poorly understood. To clarify the role of ISWI in vivo, we examined defects in chromosome structure and gene expression resulting from the loss of Iswi function in Drosophila. Consistent with a broad role in transcriptional regulation, the expression of a large number of genes is altered in Iswi mutant larvae. The expression of a dominant-negative form of ISWI leads to dramatic alterations in higher-order chromatin structure, including the apparent decondensation of both mitotic and polytene chromosomes. The loss of ISWI function does not cause obvious defects in nucleosome assembly, but results in a significant reduction in the level of histone H1 associated with chromatin in vivo. These findings suggest that ISWI plays a global role in chromatin compaction in vivo by promoting the association of the linker histone H1 with chromatin.
    [Article – URL not found]
  9. Srinivasan S, Armstrong JA, Deuring R, Dahlsveen IK, McNeill H, Tamkun JW. (2005). The Drosophila trithorax group protein Kismet facilitates an early step in transcriptional elongation by RNA Polymerase II. Development 132: 1623-1635.
    Abstract – The Drosophila trithorax group gene kismet (kis) was identified in a screen for extragenic suppressors of Polycomb (Pc) and subsequently shown to play important roles in both segmentation and the determination of body segment identities. One of the two major proteins encoded by kis (KIS-L) is related to members of the SWI2/SNF2 and CHD families of ATP-dependent chromatin-remodeling factors. To clarify the role of KIS-L in gene expression, we examined its distribution on larval salivary gland polytene chromosomes. KIS-L is associated with virtually all sites of transcriptionally active chromatin in a pattern that largely overlaps that of RNA Polymerase II (Pol II). The levels of elongating Pol II and the elongation factors SPT6 and CHD1 are dramatically reduced on polytene chromosomes from kis mutant larvae. By contrast, the loss of KIS-L function does not affect the binding of PC to chromatin or the recruitment of Pol II to promoters. These data suggest that KIS-L facilitates an early step in transcriptional elongation by Pol II.
    Article – https://dev.biologists.org/content/132/7/1623.full
  10. Armstrong JA, Sperling AS, Deuring R, Manning L, Moseley SL, Papoulas O, Piatek CI, Doe CQ, Tamkun JW. (2005). Genetic screens for enhancers of brahma reveal functional interactions between the BRM chromatin-remodeling complex and the delta-notch signal transduction pathway in Drosophila. Genetics 170: 1761-1774.
    Abstract – The Drosophila trithorax group gene brahma (brm) encodes the ATPase subunit of a 2-MDa chromatin-remodeling complex. brm was identified in a screen for transcriptional activators of homeotic genes and subsequently shown to play a global role in transcription by RNA polymerase II. To gain insight into the targeting, function, and regulation of the BRM complex, we screened for mutations that genetically interact with a dominant-negative allele of brm (brmK804R). We first screened for dominant mutations that are lethal in combination with a brmK804R transgene under control of the brm promoter. In a distinct but related screen, we identified dominant mutations that modify eye defects resulting from expression of brmK804R in the eye-antennal imaginal disc. Mutations in three classes of genes were identified in our screens: genes encoding subunits of the BRM complex (brm, moira, and osa), other proteins directly involved in transcription (zerknullt and RpII140), and signaling molecules (Delta and vein). Expression of brmK804R in the adult sense organ precursor lineage causes phenotypes similar to those resulting from impaired Delta-Notch signaling. Our results suggest that signaling pathways may regulate the transcription of target genes by regulating the activity of the BRM complex.
    Article – https://www.genetics.org/content/170/4/1761.full
  11. Corona D.F., Armstrong, J.A., and Tamkun, J.W. (2004). Genetic and Cytological Analysis of Drosophila Chromatin-Remodeling Factors. Methods in Enzymology  377: 70-85.
  12. Armstrong, J.A., Papoulas, O., Daubresse, G., Sperling, A.S., Lis, J.T., Scott, M.P., and Tamkun, J.W . (2002). The Drosophila BRM Complex Facilitates Global Transcription by RNA Polymerase II. EMBO Journal 21: 5245-5254
    Abstract – Drosophila brahma (brm) encodes the ATPase subunit of a 2 MDa complex that is related to yeast SWI/SNF and other chromatin-remodeling complexes. BRM was identified as a transcriptional activator of Hox genes required for the specification of body segment identities. To clarify the role of the BRM complex in the transcription of other genes, we examined its distribution on larval salivary gland polytene chromosomes. The BRM complex is associated with nearly all transcriptionally active chromatin in a pattern that is generally non-overlapping with that of Polycomb, a repressor of Hox gene transcription. Reduction of BRM function dramatically reduces the association of RNA polymerase II with salivary gland chromosomes. A few genes, such as induced heat shock loci, are not associated with the BRM complex; transcription of these genes is not compromised by loss of BRM function. The distribution of the BRM complex thus correlates with a dependence on BRM for gene activity. These data suggest that the chromatin remodeling activity of the BRM complex plays a general role in facilitating transcription by RNA polymerase II.
  13. Moshkin, Y.M., Armstrong, J.A., Maeda, R.K., Tamkun, J.W., Verrijzer, P., Kennison, J.A., and Karch, F . (2002). Histone Chaperone ASF1 Cooperates with the Brahma Chromatin Remodeling Machinery. Genes and Development 16: 2621-2626.
    Article – https://genesdev.cshlp.org/content/16/20/2621.full
  14. Mollaaghababa, R., Sipos, L., Tiong, S.Y.K., Papoulas, O., Armstrong, J.A., Tamkun, J. W., and Bender, W. (2001). Mutations in Drosophila heat shock cognate 4 are Enhancers of Polycomb. Proc. Natl. Acad. Sci. 98: 3958-3963.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31161/?tool=pubmed
  15. Papoulas, O., Daubresse, G., Armstrong, J.A., Jin, J., Scott, M.P., and Tamkun, J.W. (2001). The HMG-Domain Protein BAP111 Is Important for the Function of the BRM Chromatin-Remodeling Complex In Vivo. Proc. Natl. Acad. Sci.   98: 5728-5733.
    Article – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC33281/?tool=pubmed
  16. Deuring, R., Fanti, L., Armstrong, J.A., Sarte, M., Papoulas, O., Prestel, M., Daubresse, G., Verardo, M., Moseley, S.L., Berloco, M., Tsukiyama, T., Wu, C., Pimpinelli, S., and Tamkun, J.W . (2000). The ISWI Chromatin-Remodeling Protein Is Required for Gene Expression and the Maintenance of Higher Order Chromatin Structure In Vivo. Molecular Cell   5: 355-365.
    Abstract – Drosophila ISWI, a highly conserved member of the SWI2/SNF2 family of ATPases, is the catalytic subunit of three chromatin-remodeling complexes: NURF, CHRAC, and ACF. To clarify the biological functions of ISWI, we generated and characterized null and dominant-negative ISWI mutations. We found that ISWI mutations affect both cell viability and gene expression during Drosophila development. ISWI mutations also cause striking alterations in the structure of the male X chromosome. The ISWI protein does not colocalize with RNA Pol II on salivary gland polytene chromosomes, suggesting a possible role for ISWI in transcriptional repression. These findings reveal novel functions for the ISWI ATPase and underscore its importance in chromatin remodeling in vivo.
    Article – URL not found
  17. Armstrong, J.A., Bieker, J.J., and Emerson, B.M. (1998). A SWI/SNF-Related Chromatin Remodeling Complex, E-RC1, Is Required for Tissue-Specific Transcriptional Regulation by EKLF In Vitro. Cell  95: 93-104.
    Abstract – Erythroid Krüppel-like factor (EKLF) is necessary for stage-specific expression of the human -globin gene. We show that EKLF requires a SWI/SNF–related chromatin remodeling complex, E KLF coactivator-r emodeling c omplex 1 (E-RC1), to generate a DNase I hypersensitive, transcriptionally active -globin promoter on chromatin templates in vitro. E-RC1 contains BRG1, BAF170, BAF155, and INI1 (BAF47) homologs of yeast SWI/SNF subunits, as well as a subunit unique to higher eukaryotes, BAF57, which is critical for chromatin remodeling and transcription with EKLF. E-RC1 displays functional selectivity toward transcription factors, since it cannot activate expression of chromatin-assembled HIV-1 templates with the E box–binding protein TFE-3. Thus, a member of the SWI/SNF family acts directly in transcriptional activation and may regulate subsets of genes by selectively interacting with specific DNA-binding proteins.
    Article – URL not found
  18. Bagga, R., Armstrong, J.A., and Emerson, B.M. (1998). The Role of Chromatin Structure and Distal Enhancers in Tissue-Specific Transcriptional Regulation In Vitro. Cold Spring Harbor Symposia on Quantitative Biology 63: 569-576.
  19. Armstrong, J.A. and Emerson, B.M. (1998). Transcription of Chromatin: These are Complex Times. Current Opinion in Genetics and Development   8: 165-172.
    Abstract – Transcription of chromatin-packaged genes involves highly regulated changes in nucleosomal structure that control DNA accessibility. Two systems that facilitate these changes are ATP-dependent chromatin remodeling complexes and enzymatic complexes which control histone acetylation and deacetylation. Recent studies provide insight on the role of these remodeling machines and specific transcription factors in the expression of viral, inducible, and tissue-restricted genes.
  20. Armstrong, J.A. and Emerson, B.M. (1996). NF-E2 Disrupts Chromatin Structure at Human β-Globin Locus Control Region Hypersensitive Site 2 In Vitro. Molecular and Cellular Biology   16: 5634-5644.
    Abstract – The human beta-globin locus control region (LCR) is responsible for forming an active chromatin structure extending over the 100-kb locus, allowing expression of the beta-globin gene family. The LCR consists of four erythroid-cell-specific DNase I hypersensitive sites (HS1 to -4). DNase I hypersensitive sites are thought to represent nucleosome-free regions of DNA which are bound by trans-acting factors. Of the four hypersensitive sites only HS2 acts as a transcriptional enhancer. In this study, we examine the binding of an erythroid protein to its site within HS2 in chromatin in vitro. NF-E2 is a transcriptional activator consisting of two subunits, the hematopoietic cell-specific p45 and the ubiquitous DNA-binding subunit, p18. NF-E2 binds two tandem AP1-like sites in HS2 which form the core of its enhancer activity. In this study, we show that when bound to in vitro-reconstituted chromatin, NF-E2 forms a DNase I hypersensitive site at HS2 similar to the site observed in vivo. Moreover, NF-E2 binding in vitro results in a disruption of nucleosome structure which can be detected 200 bp away. Although NF-E2 can disrupt nucleosomes when added to preformed chromatin, the disruption is more pronounced when NF-E2 is added to DNA prior to chromatin assembly. Interestingly, the hematopoietic cell-specific subunit, p45, is necessary for binding to chromatin but not to naked DNA. Interaction of NF-E2 with its site in chromatin-reconstituted HS2 allows a second erythroid factor, GATA-1, to bind its nearby sites. Lastly, nucleosome disruption by NF-E2 is an ATP-dependent process, suggesting the involvement of energy-dependent nucleosome remodeling factors.
    Article – https://mcb.asm.org/content/mcb/16/10/5634.full.pdf?view=reprint&pmid=8816476
  21. Oliver, M.J., Armstrong, J., and Bewley, J.D. (1993). Desiccation and the Control of Expression of β-Phaseolin in Transgenic Tobacco Seeds. Journal of Experimental Botany 44: 1239-1244.
    Article – URL not found