Research and Teaching Interests: Epigenetics and chromatin
Office Hours: By appointment
- BS, University of Missouri Columbia, Biology (with Honors)
- PhD, Washington University in St. Louis, Evolutionary and Population Biology
Dr. Riddle obtained her undergraduate degree from the University of Missouri in Columbia, carrying out research in a maize lab. During her graduate work at Washington University in St. Louis, she first learned about epigenetics, a research field that focuses on heritable changes in phenotypes that are not associated with changes in the DNA. At the time, epigenetics was poorly understood, and her fascination with this field has grown with the scientific community’s increasing appreciation for the influence of epigenetics on other aspects of biology. In her scientific career, Dr. Riddle has studied various aspects of epigenetics in plants and animals. Her lab at UAB utilizes a classical genetics model system, the fruit fly Drosophila melanogaster, to study various open questions in the area of epigenetics and chromatin.
My research focuses on understanding the mechanisms establishing and regulating epigenetic information, and how epigenetic systems ultimately contribute to gene regulation and disease. In addition to the genetic information encoded within the DNA, other forms of information exist in the cell. Epigenetic information is heritable, affects gene expression states and phenotypes, but is independent of DNA sequence. Examples of epigenetic systems include DNA methylation, histone modifications, and chromatin structure. These epigenetic systems play vital roles in gene regulation, and defects in epigenetic regulation have been implicated in a variety of human diseases including cancer. My lab uses the fruit fly Drosophila melanogaster as a model system to investigate epigenetic systems and their influence on development and gene regulation. Currently, there are two on-going projects in the lab:
- The regulation of H3K9 methylation: H3K9 methylation is a histone mark generally associated with silent regions of the genome and heterochromatin. In many eukaryotes including Drosophila, H3K9 methylation is generated by three classes of SET domain containing histone methyltransferases. In Drosophila, the action of SU(VAR)3-9, EGG, and G9a produces the genome-wide H3K9 methylation patters. However, how the three enzymes are coordinated and what their individual roles are is poorly understood. We are using molecular genetic, biochemical, and genomics approaches to answer these questions.
- The HP1 protein family: Heterochromatin protein 1a (HP1a) was discovered as the first heterochromatin-associated protein. Its binding characterizes the heterochromatic regions of the fly genome, and homologs have been identified in species ranging from yeast to humans. The HP1a protein contains two conserved domains, the chromo domain, and the chromo-shadow domain. Based on this domain structure, four additional HP1 family proteins have been identified in Drosophila melanogaster. Of these, HP1B and HP1C, like HP1a, are ubiquitously expressed, while HP1D/RHINO and HP1E are restricted to the germline in females and males respectively. While HP1a binds large domains in heterochromatin, it also shows binding to active transcription start sites, where it is generally found in the company of HP1B and/or HP1C. We are using molecular genetic and genomics approaches to understand the relationship between HP1a, HP1B, and HP1C, and their effect on gene regulation.
- Epigenetics Discussion/Journal Club
- Tandy Dolin-Petrov
- Benjamin Mills
- Louis Watanabe
- Christine McBride
- Mills BB, McBride CL, and Riddle NC, "Epigenetic inheritance," accepted to appear in Epigenetic Gene Expression and Regulation, Huang S, Litt M, & Blakey CA, ed.
- Petrov TD, and Riddle NC, "The evolution of new technologies and methods in clinical epigenetic research," accepted to appear in Epigenetic biomarkers and diagnostics, JL Garcia-Gimenez, ed. (Elsevier AP).
- Watanabe LP, and Riddle NC, "Inter-individual variability of DNA methylation," accepted to appear in Personalized Epigenetics, Trygve Tollefsbol, ed. (Elsevier AP):17-52.
- Riddle NC, "Heritable generational epigenetic effects through RNA," in Transgenerational Epigenetics: Evidence and Debate, Trygve Tollefsbol, ed. (Elsevier AP, 2014):105-20.
- Leung W, Shaffer CD, …, Riddle NC, Buhler J, Mardis ER, and Elgin SCR, "Drosophila Muller F elements maintain a distinct set of genomic properties over 40 million years of evolution," G3 5 (No. 5, 2015):719-40.
- Ho JWK, Jung YL, Liu T, Alver BH*, Lee S*, Ikegami K*, Sohn K-A*, Minoda A*, Tolstorukov MY*, Appert A*, Parker SCJ*, Gu T*, Kundaje A*, Riddle NC*, Bishop E*, Egelhofer TA*, Hu SS*, Alekseyenko AA*, Rechtsteiner A*, Schwartz YB*, Asker D, Belsky JA, Bowman SK, Chen QB, Chen RA-J, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska-Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE, Dernburg AF, Pirrotta V, Kuroda MI, Noble WS, Tullius TD, Kellis M, MacAlpine DM, Strome S, Elgin SCR, Liu XS, Lieb JD, Ahringer J, Karpen GH, and Park PJ, "Comparative analysis of metazoan chromatin organization," Nature 512 (2014):449-52. *Co-second authors
- Riddle NC, Jung YL, Gu T, Alekseyenko AA, Asker D, Gui H, Kharchenko PV, Minoda A, Plachetka A, Schwartz YB, Tolstorukov MY, Kuroda MI, Pirrotta V, Karpen GH, Park PJ, and Elgin SCR, "Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain," PLoS Genetics 8 (No. 9, 2012):e1002954.
- Alekseyenko AA, Ho JWK, Peng S, Gelbart M, Tolstorukov MY, Plachetka A, Kharchenko PV, Jung YL, Gorchakov AA, Larschan E, Gu T, Minoda A, Riddle NC, Schwartz YB, Elgin SCR, Karpen GH, Pirrotta V, Kuroda MI, and Park PJ, "Sequence-specific targeting of dosage compensation in Drosophila favors an active chromatin context," PLoS Genetics 8 (No. 4, 2012):e1002646.
- Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC, Ernst J, Sabo PJ, Larschan E, Gorchakov AA, Gu T, Linder-Basso D, Plachetka A, Shanower GA, Tolstorukov MY, Luquette LJ, Xi R, Jung YL, Park RW, Bishop EP, Canfield TP, Sandstrom R, Thurman RE, MacAlpine DM, Stamatoyannopoulos J, Kellis M, Elgin SCR, Kuroda MI, Pirrotta V, Karpen G, and Park PJ, "Comprehensive analysis of the chromatin landscape in Drosophila melanogaster," Nature 471 (2011):480-85.
- Riddle NC*, Minoda A*, Kharchenko PV*, Alekseyenko AA, Schwartz YB, Tolstorukov MY, Gorchakov AA, Kennedy C, Linder-Basso D, Peach SE, Shanower GA, Zheng H, Jaffe JD, Kuroda MI, Pirrotta V, Park PJ, Elgin SCR, and Karpen GH, "Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin," Genome Research 21 (2011):147-63. *Co-first authors
- The modENCODE Consortium, et al., "Identification of functional elements and regulatory circuits by Drosophila modENCODE," Science 330 (2010): 1787-97. (Nicole Riddle is a current member of the modENCODE Consortium)
- Brower-Toland B*, Riddle NC*, Jiang H, Huisinga KL, and Elgin SCR, "Multiple SET methyltransferases are required to maintain normal heterochromatin domains in the genome of Drosophila melanogaster," Genetics 181 (2009):1303-19. *Co-first authors
- Riddle NC, Leung W, Haynes KA, Granok H, Wuller J, and Elgin SCR, "An investigation of heterochromatin domains on the fourth chromosome of Drosophila melanogaster," Genetics 178 (2008):1177-91.
- Named New Investigator for the UAB Nutrition Obesity Research Center (NORC), 2015
- Provost's Award for Faculty Excellence in Academic Engagement and Global Citizenship, 2014
- American Association for the Advancement of Science
- The Genetics Society of America
- Sigma Xi
- UAB Genetics Club