Peter L. Jones, Ph.D.
Principal Scientist Muscle development; Epigenetic regulation; Facioscapulohumeral muscular dystrophy; MeCP2 and Rett syndrome pjones@bbri.org
Research Summary Precise epigenetic gene and genome regulation is critical for normal development and epigenetic dysregulation is now recognized as an underlying factor in many human disorders. Our laboratory investigates two diseases whose etiologies are based in disrupted epigenetic regulation, facioscapulohumeral muscular dystrophy (FSHD) and Rett Syndrome (RTT). We combine biochemistry, molecular, cellular, and developmental biology approaches with unique animal models generated in Xenopus, Drosophila, and C. elegans to first understand the normal function of the proteins involved in these diseases and later how their disrupted regulation leads to disease pathophysiology. Along the way we are identifying new biological pathways involved in RTT progression and new biomarkers disrupted in FSHD patient skeletal muscle.
Figure 1: FSHD region
gene 1 (FRG1) overexpression leads to skeletal muscle disruption and
disorganization. This Xenopus laevis tadpole is
half-transgenic, overexpressing FRG1-EGFP from the skeletal actin promoter on
only one side (*right half).
Selected Publications Meredith Hanel, Chia-Yun Jessica Sun, Takako I. Jones, Steven E. Long, Simona Zanotti, Derek Milner, and Peter L. Jones. (2011) Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein Differentiation 81:107-118.
Steven W.
Long, Jenny Y.Y. Ooi, Peter M. Yau and Peter L. Jones. (2011) A brain-derived
methyl-CpG binding protein 2 (MeCP2) complex supports a role for MeCP2 in RNA
processing. Bioscience Reports,
31(5):333-343.
Ozren Bogdanovic, Steven W. Long, Simon van Heeringen, Arjen Brinkman, Hendrik G. Stunnenberg, Peter L. Jones, and Gert Jan C. Veenstra. (2011) Temporal uncoupling of the DNA methylome and transcriptional repression during embryogenesis. Genome Research 21:1313-1327.
Qian Liu, Takako Iida Jones, Vivian W. Tang, William M. Brieher, and Peter L. Jones (2010). Facioscapulohumeral region gene-1 (FRG-1) is an actin bundling protein associated with muscle attachment sites. Journal of Cell Science 123:1116-1123.
Ryan D. Wuebbles, Steven W. Long, Meredith L. Hanel, and Peter L. Jones (2010).Testing the effects of FSHD candidate gene expression in vertebrate development. International Journal of Clinical and Experimental Pathology 3(4):386-400.
Ryan D. Wuebbles, Meredith L. Hanel, and Peter L. Jones (2009). FSHD region gene 1 (FRG1) is crucial for angiogenesis linking FRG1 to facioscapulohumeral muscular dystrophy-associated vasculopathy. Disease Models and Mechanisms 2:267-274.
Meredith L. Hanel, Ryan D. Wuebbles, and Peter L. Jones (2009). Muscular dystrophy candidate gene FRG1 is critical for muscle development. Developmental Dynamics 238:1502-1512.
Assam El-Osta, Daniella Brasacchio, Dachun Yao, Alessandro Pocai, Peter L. Jones, Robert G. Roeder, Mark E. Cooper, and Michael Brownlee. (2008) Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. Journal of Experimental Medicine 205:2409-2417.
Ryan D. Wuebbles and Peter L. Jones (2007). Engineered telomeres in transgenic Xenopus laevis. Transgenic Research 16:377-84.
Ying Wang, Mireia Jorda, Peter L. Jones, Ryszard Maleszka, Xu Ling, Hugh M. Robertson, Craig A. Mizzen, Miguel A. Peinado, Gene E. Robinson (2006). Functional CpG methylation system in a social insect. Science 314:645-647.
KN Harikrishnan, Maggie Chow, Emma K. Baker, Sharmista Pal, Sahar Bassal, Daniella Brasacchio, Li Wang, Jeff M. Craig, Peter L. Jones, Said Sif, and Assam El-Osta (2005). Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing. Nature Genetics. 37:254-64.
Peter L. Jones, Laurent M. Sachs, Nicole Rouse, Paul A. Wade, and Yun-Bo Shi (2001). Multiple N-CoR complexes contain distinct histone deacetylases. J. Biol. Chem. 276:8807-8812.
Paul A. Wade, Peter L. Jones, Danielle Vermaak, and Alan P. Wolffe (1998). A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase. Current Biology, 8:843-846.
Peter L. Jones, Gert Jan C. Veenstra, Paul A. Wade, Danielle Vermaak, Stefan U. Kass, Nicoletta Landsberger, John Strouboulis, and Alan P. Wolffe (1998). Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nature Genetics, 19:187-191.
Peter L. Jones, Dongsheng Ping, and Jeremy M. Boss (1997). Tumor necrosis factor-a and Interleukin-1b regulate the murine manganese superoxide dismutase gene through a complex intronic enhancer involving C/EBP-b and NF-kB. Molecular and Cellular Biology, 17:6970-6981.
PubMed: |
