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3258 TAMU Office: Lab: Fax: 979-845-2891 |
Biography |
| Keith Maggert received his bachelors degree in Biochemistry and Molecular Biology from the University of California Santa Cruz, which he attended from 1988-1992. After graduation, he entered the University of California San Diego as a graduate student. Initially, he joined the laboratory of Dr. Michael Levine and worked on mesoderm determination and gastrulation in the fruit fly, Drosophila melanogaster. After a few years, his attention turned toward chromosome biology and cytogenetics. He moved to the Salk Institute to work with Dr. Gary Karpen on the structure of the centromere - the region of the chromosome responsible for proper segregation of the genetic material. His research helped establish that identical DNA sequences may behave differently depending on context and condition, a branch of genetics called "epigenetics." This work earned him his Ph.D. in 2000. Keith continued investigating epigenetics when he joined Kent Golic's laboratory at the University of Utah in 2000 as a postdoctoral fellow. There (and during a brief visiting researcher position with John Tamkun at the University of California Santa Cruz) he began his work on genomic imprinting, asymmetric gene regulation, and DNA modification. Keith joined the faculty of the Department of Biology at Texas A&M University in the Fall of 2004. | |
| Epigenetics in Drosophila | |
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Research in my laboratory uses the fruit fly Drosophila melanogaster to investigate how a chromosome retains a memory or "imprint" of the parent from which it came, and why such an imprint may lead to different genetic properties in the organism. This genomic imprinting is a dramatic example of how genetic information can be carried by chromosomes and yet not coded by the sequence of the DNA. Although the majority of information is coded by sequence, some information is carried by the proteins that associate with the chromosome, or by DNA modification, which can cause otherwise-identical genes to behave quite differently. These differences have exciting implications for mechanisms of evolution or disease in all organisms. Genomic Imprinting: Most diploid organisms have two copies of every gene, and generally these genes behave in the same way. However, a subset of genes may behave differently if they are derived from a male (paternally-inherited) rather than from a female (maternally-inherited). This set of genes is "genomically imprinted." This phenomenon is as widespread as it is odd, being observed in plants, mammals, and insects. My research has shown that the X and Y chromosomes of Drosophila exhibit this behavior. Hence, genetically-identical organisms can exhibit vastly different phenotypes, depending on their patterns of chromosome inheritance. This type of gene regulation is known to be defective in some human diseases, including cancer. Drosophila serves as an ideal system in which to perform exploratory experiments to identify the factors that are defective in these disease states. Currently, my research is directed at identifying genes which are required to establish, maintain, or interpret the differences between paternal and maternal chromosomes. DNA Modification: Some genomic imprinting information is carried by chromosomes through modification of the DNA structure. In some cases, this modification of the DNA is by addition of a methyl group to cytosine bases. In many organisms - including yeast, fish, plants, insects, bacteria, and mammals - specific enzymes are known to catalyze this modification; these enzymes are collectively called DNA methyltransferases. Only one DNA methyltransferase, called Mt2, has been identified in Drosophila . Using homologous recombination, I have targeted Mt2 for disruption, generating a mutation that lacks activity. The mutant Mt2 is viable and fertile, but is defective in its ability to maintain paternal genomic imprints. Work in my lab is currently directed at identifying the methylation targets of Mt2, understanding how Mt2 activity is regulated differently on maternal and paternal chromosomes, and understanding how DNA methylation controls gene expression. Genomic Imprinting and Its Relationship to Evolution and Disease: Since genomic imprinting yields quantitative differences in gene expression, genomic imprinting may affect the evolution of populations of interbreeding organisms in unexpected ways. For instance, the imprinted Drosophila Y chromosome carries genes required for male fertility, and differences in paternal imprinting may affect the fertility of a male's sons. The Y chromosome also acts as a sink for potentially-destructive transposable elements, and it may be that genomic imprinting is required to inactivate these parasitic DNAs. Since epigenetic modifications are able to be reset quickly in response to such environmental stimuli as temperature and population size, it is possible that epigenetics and genomic imprinting may serve as a substrate for genetic-environment interaction. To this end, I am investigating the possible sensitivity of genomic imprinting to environmental toxins such as heavy metals and known carcinogens. |
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| Selected Publications | |
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Maggert KA, Gong WJ, Golic KG. ( in press). "Methods for Homologous Recombina- tion in Drosophila," in Drosophila Protocols, Christian Dahmann editor. Humana Press. Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh C-L, Zhang X, Golic KG, Jacobsen SE, Bestor TH. (2006). Methylation of tRNAAsp by DNA methyltransferase-2 in mammals, flowering plants, and Dipteran insects. Science, 311: 395-398. Maggert K, Golic K. (2005). Highly-Efficient Sex Chromosome Interchanges Produced by I-CreI Expression in Drosophila. Genetics, 171: 1103-1114. Maggert, Keith and Kent Golic. (2005). Highly-efficient sex chromosome interchanges produced by I-CreI expression in Drosophila. Genetics, in press. Maggert, Keith and Kent Golic. (2002). The Y Chromosome of Drosophila melanogaster Exhibits Chromosome-Wide Imprinting . Genetics, 162(3): 1245-1258. Maggert, Keith and Gary Karpen. (2001). The Activation of a Neocentromere in Drosophila Requires Proximity to an Endogenous Centromere . Genetics, 158(4): 1615-1628. Maggert, Keith and Gary Karpen. (2000). Acquisition and metastability of centromere identity and function: sequence analysis of a human neocentromere . Genome Research, 10: 725-728. Dobie, Kenneth, Kumar Hari, Keith Maggert and Gary Karpen. (1999). Centromere proteins and chromosome inheritance: a complex affair . Current Opinion in Genetics & Development, 9: 206-217. Maggert, Keith, Michael Levine and Manfred Frasch. (1995). The somatic-visceral subdivision of the embryonic mesoderm is initiated by dorsal gradient thresholds in Drosophila. Development, 121: 2107-2116. Ip, Y. Tony, Keith Maggert and Michael Levine. (1994). Uncoupling gastrulation and mesoderm differentiation in the Drosophila embryo . EMBO Journal, 13(24): 5826-5834. Taiz, Lincoln, Hannah Nelson, Keith Maggert, Louis Morgan, Brad Yatabe, Saundra Lee Taiz, Bernard Rubinstein and Nathan Nelson. (1994). Functional analysis of conserved cysteine residues in the catalytic subunit of the yeast vacuolar H + -ATPase . Biochimica et Biophysica Acta, 1194(2): 329-34. |
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