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Developmental Biology

University of Massachusetts Medical School

Peter Jones Lab Publications

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Articles 1 - 8 of 8

Full-Text Articles in Molecular Biology

Transgenic Drosophila For Investigating Dux4 And Frg1, Two Genes Associated With Facioscapulohumeral Muscular Dystrophy (Fshd), Takako I. Jones, Megan Parilla, Peter L. Jones Mar 2016

Transgenic Drosophila For Investigating Dux4 And Frg1, Two Genes Associated With Facioscapulohumeral Muscular Dystrophy (Fshd), Takako I. Jones, Megan Parilla, Peter L. Jones

Peter Jones Lab Publications

Facioscapulohumeral muscular dystrophy (FSHD) is typically an adult onset dominant myopathy. Epigenetic changes in the chromosome 4q35 region linked to both forms of FSHD lead to a relaxation of repression and increased somatic expression of DUX4-fl (DUX4-full length), the pathogenic alternative splicing isoform of the DUX4 gene. DUX4-fl encodes a transcription factor expressed in healthy testis and pluripotent stem cells; however, in FSHD, increased levels of DUX4-fl in myogenic cells lead to aberrant regulation of target genes. DUX4-fl has proven difficult to study in vivo; thus, little is known about its normal and pathogenic roles. The endogenous expression of DUX4-fl ...


Association Of Modified Cytosines And The Methylated Dna-Binding Protein Mecp2 With Distinctive Structural Domains Of Lampbrush Chromatin, Garry T. Morgan, Peter L. Jones, Michel Bellini Dec 2012

Association Of Modified Cytosines And The Methylated Dna-Binding Protein Mecp2 With Distinctive Structural Domains Of Lampbrush Chromatin, Garry T. Morgan, Peter L. Jones, Michel Bellini

Peter Jones Lab Publications

We have investigated the association of DNA methylation and proteins interpreting methylation state with the distinctive closed and open chromatin structural domains that are directly observable in the lampbrush chromosomes (LBCs) of amphibian oocytes. To establish the distribution in LBCs of MeCP2, one of the key proteins binding 5-methylcytosine-modified DNA (5mC), we expressed HA-tagged MeCP2 constructs in Xenopus laevis oocytes. Full-length MeCP2 was predominantly targeted to the closed, transcriptionally inactive chromomere domains in a pattern proportional to chromomeric DNA density and consistent with a global role in determining chromatin state. A minor fraction of HA-MeCP2 was also found to associate ...


C. Elegans Pat-9 Is A Nuclear Zinc Finger Protein Critical For The Assembly Of Muscle Attachments, Qian Liu, Takako I. Jones, Rebecca A. Bachmann, Mitchell Meghpara, Lauren Rogowski, Benjamin D. Williams, Peter L. Jones May 2012

C. Elegans Pat-9 Is A Nuclear Zinc Finger Protein Critical For The Assembly Of Muscle Attachments, Qian Liu, Takako I. Jones, Rebecca A. Bachmann, Mitchell Meghpara, Lauren Rogowski, Benjamin D. Williams, Peter L. Jones

Peter Jones Lab Publications

BACKGROUND: Caenorhabditis elegans sarcomeres have been studied extensively utilizing both forward and reverse genetic techniques to provide insight into muscle development and the mechanisms behind muscle contraction. A previous genetic screen investigating early muscle development produced 13 independent mutant genes exhibiting a Pat (paralyzed and arrested elongation at the two-fold length of embryonic development) muscle phenotype. This study reports the identification and characterization of one of those genes, pat-9.

RESULTS: Positional cloning, reverse genetics, and plasmid rescue experiments were used to identify the predicted C. elegans gene T27B1.2 (recently named ztf-19) as the pat-9 gene. Analysis of pat-9 showed ...


A Brain-Derived Mecp2 Complex Supports A Role For Mecp2 In Rna Processing, Steven W. Long, Jenny Y. Y. Ooi, Peter M. Yau, Peter L. Jones Oct 2011

A Brain-Derived Mecp2 Complex Supports A Role For Mecp2 In Rna Processing, Steven W. Long, Jenny Y. Y. Ooi, Peter M. Yau, Peter L. Jones

Peter Jones Lab Publications

Mutations in MECP2 (methyl-CpG-binding protein 2) are linked to the severe postnatal neurodevelopmental disorder RTT (Rett syndrome). MeCP2 was originally characterized as a transcriptional repressor that preferentially bound methylated DNA; however, recent results indicate MeCP2 is a multifunctional protein. MeCP2 binding is now associated with certain expressed genes and involved in nuclear organization as well, indicating that its gene regulatory function is context-dependent. In addition, MeCP2 is proposed to regulate mRNA splicing and a mouse model for RTT shows aberrant mRNA splicing. To further understand MeCP2 and potential roles in RTT pathogenesis, we have employed a biochemical approach to identify ...


Temporal Uncoupling Of The Dna Methylome And Transcriptional Repression During Embryogenesis, Ozren Bogdanovic, Steven W. Long, Simon J. Van Heeringen, Arie B. Brinkman, Jose Luis Gomez-Skarmeta, Hendrik G. Stunnenberg, Peter L. Jones, Gert Jan C. Veenstra Aug 2011

Temporal Uncoupling Of The Dna Methylome And Transcriptional Repression During Embryogenesis, Ozren Bogdanovic, Steven W. Long, Simon J. Van Heeringen, Arie B. Brinkman, Jose Luis Gomez-Skarmeta, Hendrik G. Stunnenberg, Peter L. Jones, Gert Jan C. Veenstra

Peter Jones Lab Publications

DNA methylation is a tightly regulated epigenetic mark associated with transcriptional repression. Next-generation sequencing of purified methylated DNA obtained from early Xenopus tropicalis embryos demonstrates that this genome is heavily methylated during blastula and gastrula stages. Although DNA methylation is largely absent from transcriptional start sites marked with histone H3 lysine 4 trimethylation (H3K4me3), we find both promoters and gene bodies of active genes robustly methylated. In contrast, DNA methylation is absent in large H3K27me3 domains, indicating that these two repression pathways have different roles. Comparison with chromatin state maps of human ES cells reveals strong conservation of epigenetic makeup ...


Fshd Region Gene 1 (Frg1) Is Crucial For Angiogenesis Linking Frg1 To Facioscapulohumeral Muscular Dystrophy-Associated Vasculopathy, Ryan Wuebbles, Meredith L. Hanel, Peter L. Jones May 2009

Fshd Region Gene 1 (Frg1) Is Crucial For Angiogenesis Linking Frg1 To Facioscapulohumeral Muscular Dystrophy-Associated Vasculopathy, Ryan Wuebbles, Meredith L. Hanel, Peter L. Jones

Peter Jones Lab Publications

The genetic lesion that is diagnostic for facioscapulohumeral muscular dystrophy (FSHD) results in an epigenetic misregulation of gene expression, which ultimately leads to the disease pathology. FRG1 (FSHD region gene 1) is a leading candidate for a gene whose misexpression might lead to FSHD. Because FSHD pathology is most prominent in the musculature, most research and therapy efforts focus on muscle cells. Previously, using Xenopus development as a model, we showed that altering frg1 expression levels systemically leads to aberrant muscle development, illustrating the potential for aberrant FRG1 levels to disrupt the musculature. However, 50-75% of FSHD patients also exhibit ...


Transient High Glucose Causes Persistent Epigenetic Changes And Altered Gene Expression During Subsequent Normoglycemia, Assam El-Osta, Daniella Brasacchio, Dachun Yao, Alessandro Pocai, Peter L. Jones, Robert G. Roeder, Mark E. Cooper, Michael Brownlee Sep 2008

Transient High Glucose Causes Persistent Epigenetic Changes And Altered Gene Expression During Subsequent Normoglycemia, Assam El-Osta, Daniella Brasacchio, Dachun Yao, Alessandro Pocai, Peter L. Jones, Robert G. Roeder, Mark E. Cooper, Michael Brownlee

Peter Jones Lab Publications

The current goal of diabetes therapy is to reduce time-averaged mean levels of glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c only explains <25% of the variation in risk of developing complications. Because HbA1c does not correlate with glycemic variability when adjusted for mean blood glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c-independent risk factor for diabetic complications. We show that transient hyperglycemia induces long-lasting activating epigenetic changes in the promoter of the nuclear factor kappaB (NF-kappaB) subunit p65 in aortic endothelial cells both in vitro and in nondiabetic mice, which cause increased p65 gene expression. Both the epigenetic changes and the gene expression changes persist for at least 6 d of subsequent normal glycemia, as do NF-kappaB-induced increases in monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression. Hyperglycemia-induced epigenetic changes and increased p65 expression are prevented by reducing mitochondrial superoxide production or superoxide-induced alpha-oxoaldehydes. These results highlight the dramatic and long-lasting effects that short-term hyperglycemic spikes can have on vascular cells and suggest that transient spikes of hyperglycemia may be an HbA1c-independent risk factor for diabetic complications.


The Tripartite Motif (Trim) Of Nuclear Factor 7 Is Required For Its Association With Transcription Units, Brent Beenders, Peter L. Jones, Michel Bellini Apr 2007

The Tripartite Motif (Trim) Of Nuclear Factor 7 Is Required For Its Association With Transcription Units, Brent Beenders, Peter L. Jones, Michel Bellini

Peter Jones Lab Publications

In amphibian oocytes, the maternal nuclear factor NF7 associates with the elongating pre-mRNAs present on the numerous lateral loops of the lampbrush chromosomes. Here, we have purified NF7 from an oocyte extract by using a combination of ion-exchange chromatography and gel filtration chromatography and demonstrated for the first time that nucleoplasmic NF7 exists primarily as free homotrimers. We confirmed the in vivo homotrimerization of NF7 by using a glutaraldehyde cross-linking assay, and we further showed that it only requires the coiled-coil domain of the NF7 tripartite motif/RBCC motif. Interestingly, we also obtained evidence that NF7 is recruited to the ...