Keith A Maggert

Keith A Maggert
The University of Arizona | UA · Department of Cellular and Molecular Medicine

PhD

About

37
Publications
5,564
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Introduction
Keith A Maggert currently works at the Department of Cellular and Molecular Medicine, The University of Arizona. Keith does research in Molecular Biology, Developmental Biology and Genetics. His particular expertise is in epigenetics, heterochromatin biology, and the ribosomal DNA (rDNA). He likes espresso and dogs, and reads old papers for fun.
Additional affiliations
January 2015 - present
The University of Arizona
Position
  • Professor (Associate)
September 2011 - December 2015
Texas A&M University
Position
  • Professor (Associate)
September 2004 - September 2011
Texas A&M University
Position
  • Professor (Assistant)
Education
September 1992 - May 2000
September 1988 - June 1992
University of California, Santa Cruz
Field of study
  • Biochemistry and Molecular Biology

Publications

Publications (37)
Article
Position-effect variegation (PEV) results from the juxtaposition of euchromatic and heterochromatic components of eukaryotic genomes, silencing genes near the new euchromatin/heterochromatin junctions. Silencing is itself heritable through S phase, giving rise to distinctive random patterns of cell clones expressing the genes intermixed with clones...
Article
The ribosomal DNA (rDNA) in Drosophila is found as two additive clusters of individual 35 S cistrons. The multiplicity of rDNA is essential to assure proper translational demands, but the nature of the tandem arrays expose them to copy number variation within and between populations. Here, we discuss means by which a cell responds to insufficient r...
Article
Full-text available
Position effect variegation (PEV) in Drosophila results from new juxtapositions of euchromatic and heterochromatic chromosomal regions, and manifests as striking bimodal patterns of gene expression. The semirandom patterns of PEV, reflecting clonal relationships between cells, have been interpreted as gene-expression states that are set in developm...
Article
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Article
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Chromatin-mediated silencing, including the formation of heterochromatin, silent chromosome territories, and repressed gene promoters, acts to stabilize patterns of gene regulation and the physical structure of the genome. Reduction of chromatin-mediated silencing can result in genome rearrangements, particularly at intrinsically unstable regions o...
Article
Full-text available
The Pol32 protein is one of the universal subunits of DNA polymerase δ (Pol δ), which is responsible for genome replication in eukaryotic cells. Although the role of Pol32 in DNA repair has been well-characterized, its exact function in genome replication remains obscure as studies in single cell systems have not established an essential role for P...
Preprint
Full-text available
Epigenetic silencing, including the formation of heterochromatin, silent chromosome territories, and repressed gene promoters, acts to stabilize patterns of gene regulation and the physical structure of the genome. Reduction of epigenetic silencing can result in genome rearrangements, particularly at intrinsically unstable regions of the genome suc...
Article
Full-text available
Our goal is to draw a line—hypothetical in its totality but experimentally supported at each individual step—connecting the ribosomal DNA and the phenomenon of transgenerational epigenetic inheritance of induced phenotypes. The reasonableness of this hypothesis is offset by its implication, that many (or most) (or all) of the cases of induced-and-i...
Article
Full-text available
Interest in the field of epigenetics has increased rapidly over the last decade, with the term becoming more identifiable in biomedical research, scientific fields outside of the molecular sciences, such as ecology and physiology, and even mainstream culture. It has become increasingly clear, however, that different investigators ascribe different...
Article
Full-text available
Ribosomal RNA gene (rDNA) copy number variation modulates heterochromatin formation and influences the expression of a large fraction of the Drosophila ge-nome. This discovery, along with the link between rDNA, aging, and disease, high-lights the importance of understanding how natural rDNA copy number variation arises. Pursuing the relationship be...
Article
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Heterochromatin is a significant component of the human genome and the genomes of most model organisms. Although heterochromatin is thought to be largely non-coding, it is clear that it plays an important role in chromosome structure and gene regulation. Despite a growing awareness of its functional significance, the repetitive sequences underlying...
Article
Full-text available
The ribosomal DNA (rDNA) arrays are causal agents in X-Y chromosome pairing in meiosis-I of Drosophila males. Despite broad variation in X- and Y-linked rDNA copy number, polymorphisms in regulatory/spacer sequences between rRNA genes, and variance in copy number of interrupting R1 and R2 retrotransposable elements, there is little evidence that di...
Article
Full-text available
At its broadest sense, to say that a phenotype is epigenetic suggests that it occurs without changes in DNA sequence, yet is heritable through cell division and occasionally from one organismal generation to the next. Since gene regulatory changes are oftentimes in response to environmental stimuli and may be retained in descendent cells, there is...
Data
(A) Array design for comparing males. rDNA sizes were determined at the onset of the experiments. rDNA-mild-1 is approximately 87% the wild-type size, rDNA-mild-2 is 85% the wild-type size, and rDNA-gross is 46% the wild-type size (Figure 6). Lines are direct comparisons and indicate number of replicates. (B) Array design for comparing females. (0....
Data
(A) Expectation of overlap at P<0.01 based on chance alone. cf. Figure 2B. (B) Data from Figure 2A at P<0.005 versus values expected by chance alone. (B) Data from Figure 2A at P<0.005 versus values expected by chance alone. (C) For P<0.001. cf. Figure 2B, 2C. (0.47 MB TIF)
Data
(A) Ratio of number of differentially expressed genes to total number of genes on the microarray (data from Figure 3B). Solid horizontal line shows the average, dotted lines show two standard deviations. (B) Cumulative counts of differentially expressed genes between YrDNA-gross and wild-type Y (at P<0.01) in males (black), females (gray), and fema...
Data
(A) Observed number of shared differentially expressed genes across pairwise chromosome comparisons. P<0.05 data are shown above the diagonal, P<0.005 are shown below the diagonal, and total number (shared plus unique) of differentially expressed genes (P<0.05/P<0.005) are shown on the diagonal (bold, gray background). (B) Expected numbers of genes...
Data
(A) Crossing scheme to introgress Y chromosomes to a common and isogenic genetic background. y (yellow), bw (brown), e (ebony), ci (cubitus interruptus), ey (eyeless) were used as recessive genetic markers. (B) Crossing scheme to generate XX/Y aneuploid females. Circle represents common centromere linking compound-X chromosome arms. (0.30 MB TIF)
Data
(A) Number of differentially expressed genes (at P<0.01), broken down by decile “fold-changes” along the abscissa for the YrDNA-gross deleted chromosome, presented as absolute counts (solid lines and ordinal values) and cumulative percentage (dotted lines at 20% increments). (B) Data from (A) graphed as separate deciles to show quality of estimatio...
Data
Correlation of log-fold-changes comparing differentially expressed genes between YrDNA-gross and the wild-type Y in males (abscissa) to those differentially expressed between YrDNA-gross and the wild-type Y in females (ordinate); ρ = 0.45, P<0.0001. (0.22 MB TIF)
Article
Full-text available
The ribosomal rDNA gene array is an epigenetically-regulated repeated gene locus. While rDNA copy number varies widely between and within species, the functional consequences of subtle copy number polymorphisms have been largely unknown. Deletions in the Drosophila Y-linked rDNA modifies heterochromatin-induced position effect variegation (PEV), bu...
Article
Full-text available
In the repeat array of ribosomal DNA (rDNA), only about half of the genes are actively transcribed while the others are silenced. In arthropods, transposable elements interrupt a subset of genes, often inactivating transcription of those genes. Little is known about the establishment or separation of juxtaposed active and inactive chromatin domains...
Article
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Induction of gene expression is correlated with alterations in nuclear organization, including proximity to other active genes, to the nuclear cortex, and to cytologically distinct domains of the nucleus. Chromosomes are tethered to the insoluble nuclear scaffold/matrix through interaction with Scaffold/Matrix Attachment Region (SAR/MAR) binding pr...
Article
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The 35S ribosomal RNA genes (rDNA) are organized as repeated arrays in many organisms. Epigenetic regulation of transcription of the rRNA results in only a subset of copies being transcribed, making rDNA an important model for understanding epigenetic chromatin modification. We have created an allelic series of deletions within the rDNA array of th...
Article
Full-text available
The rDNA arrays in Drosophila contain the cis-acting nucleolus organizer regions responsible for forming the nucleolus and the genes for the 28S, 18S, and 5.8S/2S RNA components of the ribosomes and so serve a central role in protein synthesis. Mutations or alterations that affect the nucleolus organizer region have pleiotropic effects on genome re...
Article
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We present detailed protocols for two methods of gene targeting in Drosophila. The first, ends-out targeting, is identical in concept to gene replacement techniques used routinely in mammalian and yeast cells. In Drosophila, the targeted gene is replaced by the marker gene white + (although options exist to generate unmarked targeted alleles). This...
Article
Full-text available
The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases. A combined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid transfer RNA (tRNAAsp) and that...
Article
Full-text available
The homing endonuclease I-CreI recognizes a site in the gene encoding the 23S rRNA of Chlamydomonas reinhardtii. A very similar sequence is present in the 28S rRNA genes that are located on the X and Y chromosomes of Drosophila melanogaster. In this work we show that I-CreI expression in Drosophila is capable of causing induced DNA damage and elici...
Article
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Genomic imprinting is well known as a regulatory property of a few specific chromosomal regions and leads to differential behavior of maternally and paternally inherited alleles. We surveyed the activity of two reporter genes in 23 independent P-element insertions on the heterochromatic Y chromosome of Drosophila melanogaster and found that all but...
Article
Full-text available
The centromere is essential for proper segregation and inheritance of genetic information. Centromeres are generally regulated to occur exactly once per chromosome; failure to do so leads to chromosome loss or damage and loss of linked genetic material. The mechanism for faithful regulation of centromere activity and number is unknown. The presence...
Article
The centromere is essential for proper segregation and inheritance of genetic information. Centromeres are generally regulated to occur exactly once per chromosome; failure to do so leads to chromosome loss or damage and loss of linked genetic material. The mechanism for faithful regulation of centromere activity and number is unknown. The presence...
Article
Centromeres and the associated kinetochores are involved in essential aspects of chromosome transmission. Recent advances have included the identification and understanding of proteins that have a pivotal role in centromere structure, kinetochore formation, and the coordination of chromosome inheritance with the cell cycle in several organisms. A p...
Article
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The maternal dorsal regulatory gradient initiates the differentiation of the mesoderm, neuroectoderm and dorsal ectoderm in the early Drosophila embryo. Two primary dorsal target genes, snail (sna) and decapentaplegic (dpp), define the limits of the presumptive mesoderm and dorsal ectoderm, respectively. Normally, the sna expression pattern encompa...
Article
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In Drosophila, ventral furrow formation and mesoderm differentiation are initiated by two regulatory genes, twist (twi) and snail (sna). Both genes are evolutionarily conserved and have also been implicated in vertebrate gastrulation. Evidence is presented that sna is sufficient to initiate the invagination of the ventral-most embryonic cells in th...
Article
The A subunit of the yeast vacuolar ATPase contains three highly conserved cysteines: Cys-261, Cys-284, and Cys-538. Cys-261 is located within the nucleotide-binding P-loop. Each of the conserved cysteines, and one nonconserved cysteine, Cys-254, were altered to serine by site-directed mutagenesis, and the effects on growth at pH 7.5 were determine...
Article
Full-text available
Vita. Thesis (Ph. D.)--University of California, San Diego, 2000. Includes bibliographical references (leaves 137-150).

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