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Full-Text Articles in Genetics and Genomics
Trip/Nopo E3 Ubiquitin Ligase Promotes Ubiquitylation Of Dna Polymerase Η, Heather A. Wallace, Julie A. Merkle, Michael C. Yu, Taloa G. Berg, Ethan Lee, Giovanni Bosco, Laura A. Lee
Trip/Nopo E3 Ubiquitin Ligase Promotes Ubiquitylation Of Dna Polymerase Η, Heather A. Wallace, Julie A. Merkle, Michael C. Yu, Taloa G. Berg, Ethan Lee, Giovanni Bosco, Laura A. Lee
Dartmouth Scholarship
We previously identified a Drosophila maternal effect-lethal mutant named ‘no poles’ (nopo). Embryos from nopo females undergo mitotic arrest with barrel-shaped, acentrosomal spindles during the rapid cycles of syncytial embryogenesis because of activation of a Chk2-mediated DNA checkpoint. NOPO is the Drosophila homolog of human TNF receptor associated factor (TRAF)-interacting protein (TRIP), which has been implicated in TNF signaling. NOPO and TRIP contain RING domains closely resembling those of known E3 ubiquitin ligases. We herein sought to elucidate the mechanism by which TRIP/NOPO promotes genomic stability by performing a yeast two-hybrid screen to identify potential substrates/interactors. We identified members of …
Catp-6, A C. Elegans Ortholog Of Atp13a2 Park9, Positively Regulates Gem-1, An Slc16a Transporter, Eric J. Lambie, Pamela J. Tieu, Nadja Lebedeva, Diane L. Church, Barbara Conradt
Catp-6, A C. Elegans Ortholog Of Atp13a2 Park9, Positively Regulates Gem-1, An Slc16a Transporter, Eric J. Lambie, Pamela J. Tieu, Nadja Lebedeva, Diane L. Church, Barbara Conradt
Dartmouth Scholarship
In previous work, we found that gain-of-function mutations that hyperactivate GEM-1 (an SLC16A transporter protein) can bypass the requirement for GON-2 (a TRPM channel protein) during the initiation of gonadogenesis in C. elegans . Consequently, we proposed that GEM-1 might function as part of a Mg 2 + uptake pathway that functions in parallel to GON- 2. In this study, we report that CATP-6, a C. elegans ortholog of the P5B ATPase, ATP13A2 (PARK9), is necessary for gem-1 gain-of-function mutations to suppress the effects of gon-2 inactivation. One possible explanation for this observation is that GEM-1 serves to activate CATP-6, …
Temporal Regulation Of The Muscle Gene Cascade By Macho1 And Tbx6 Transcription Factors In Ciona Intestinalis, Jamie E. Kugler, Stefan Gazdoiu, Izumi Oda-Ishii, Yale J. Passamaneck, Albert J. Erives, Anna Di Gregorio
Temporal Regulation Of The Muscle Gene Cascade By Macho1 And Tbx6 Transcription Factors In Ciona Intestinalis, Jamie E. Kugler, Stefan Gazdoiu, Izumi Oda-Ishii, Yale J. Passamaneck, Albert J. Erives, Anna Di Gregorio
Dartmouth Scholarship
For over a century, muscle formation in the ascidian embryo has been representative of 'mosaic' development. The molecular basis of muscle-fate predetermination has been partly elucidated with the discovery of Macho1, a maternal zinc-finger transcription factor necessary and sufficient for primary muscle development, and of its transcriptional intermediaries Tbx6b and Tbx6c. However, the molecular mechanisms by which the maternal information is decoded by cis-regulatory modules (CRMs) associated with muscle transcription factor and structural genes, and the ways by which a seamless transition from maternal to zygotic transcription is ensured, are still mostly unclear. By combining misexpression assays with CRM analyses, …
Mir319a Targeting Of Tcp4 Is Critical For Petal Growth And Development In Arabidopsis, Anwesha Nag, Stacey King, Thomas Jack
Mir319a Targeting Of Tcp4 Is Critical For Petal Growth And Development In Arabidopsis, Anwesha Nag, Stacey King, Thomas Jack
Dartmouth Scholarship
In a genetic screen in a drnl-2 background, we isolated a loss-of-function allele in miR319a (miR319a129). Previously, miR319a has been postulated to play a role in leaf development based on the dramatic curled-leaf phenotype of plants that ectopically express miR319a (jaw-D). miR319a129 mutants exhibit defects in petal and stamen development; petals are narrow and short, and stamens exhibit defects in anther development. The miR319a129 loss-of-function allele contains a single-base change in the middle of the encoded miRNA, which reduces the ability of miR319a to recognize targets. Analysis of the expression patterns of the …
Decreased Replication Origin Activity In Temporal Transition Regions, Zeqiang Guan, Christina M. Hughes, Settapong Kosiyatrakul, Paolo Norio, Ranjan Sen, Steven Fiering
Decreased Replication Origin Activity In Temporal Transition Regions, Zeqiang Guan, Christina M. Hughes, Settapong Kosiyatrakul, Paolo Norio, Ranjan Sen, Steven Fiering
Dartmouth Scholarship
In the mammalian genome, early- and late-replicating domains are often separated by temporal transition regions (TTRs) with novel properties and unknown functions. We identified a TTR in the mouse immunoglobulin heavy chain (Igh) locus, which contains replication origins that are silent in embryonic stem cells but activated during B cell development. To investigate which factors contribute to origin activation during B cell development, we systematically modified the genetic and epigenetic status of the endogenous Igh TTR and used a single-molecule approach to analyze DNA replication. Introduction of a transcription unit into the Igh TTR, activation of gene transcription, …
Evolution Acts On Enhancer Organization To Fine-Tune Gradient Threshold Readouts, Justin Crocker, Yoichiro Tamori, Albert Erives
Evolution Acts On Enhancer Organization To Fine-Tune Gradient Threshold Readouts, Justin Crocker, Yoichiro Tamori, Albert Erives
Dartmouth Scholarship
The elucidation of principles governing evolution of gene regulatory sequence is critical to the study of metazoan diversification. We are therefore exploring the structure and organizational constraints of regulatory sequences by studying functionally equivalent cis-regulatory modules (CRMs) that have been evolving in parallel across several loci. Such an independent dataset allows a multi-locus study that is not hampered by nonfunctional or constrained homology. The neurogenic ectoderm enhancers (NEEs) of Drosophila melanogaster are one such class of coordinately regulated CRMs. The NEEs share a common organization of binding sites and as a set would be useful to study the relationship …
Ovarian Development In Mice Requires The Gata4-Fog2 Transcription Complex, Nikolay L. Manuylov, Fatima O. Smagulova, Lyndsay Leach, Sergei G. Tevosian
Ovarian Development In Mice Requires The Gata4-Fog2 Transcription Complex, Nikolay L. Manuylov, Fatima O. Smagulova, Lyndsay Leach, Sergei G. Tevosian
Dartmouth Scholarship
We have demonstrated previously that mammalian sexual differentiation requires both the GATA4 and FOG2 transcriptional regulators to assemble the functioning testis. Here we have determined that the sexual development of female mice is profoundly affected by the loss of GATA4-FOG2 interaction. We have also identified the Dkk1 gene, which encodes a secreted inhibitor of canonical beta-catenin signaling, as a target of GATA4-FOG2 repression in the developing ovary. The tissue-specific ablation of the beta-catenin gene in the gonads disrupts female development. In Gata4(ki/ki); Dkk1(-/-) or Fog2(-/-); Dkk1(-/-) embryos, the normal ovarian gene expression pattern is partially restored. Control of ovarian development …
Coordinated Regulation Of Myc Trans-Activation Targets By Polycomb And The Trithorax Group Protein Ash1, Julie M. Goodliffe, Michael D. Cole, Eric Wieschaus
Coordinated Regulation Of Myc Trans-Activation Targets By Polycomb And The Trithorax Group Protein Ash1, Julie M. Goodliffe, Michael D. Cole, Eric Wieschaus
Dartmouth Scholarship
The Myc oncoprotein is a transcriptional regulator whose function is essential for normal development. Myc is capable of binding to 10% of the mammalian genome, and it is unclear how a developing embryo controls the DNA binding of its abundant Myc proteins in order to avoid Myc's potential for inducing tumorigenesis.To identify chromatin binding proteins with a potential role in controlling Myc activity, we established a genetic assay for dMyc activity in Drosophila. We conducted a genome-wide screen using this assay, and identified the Trithorax Group protein Ash1 as a modifier of dMyc activity. Ash1 is a histone methyltransferase known …