Personnel
Lindsay S. Shopland
Institute for Molecular Biophysics
The Jackson Laboratory
(207) 288-6739
lindsay.shopland@jax.org
http://www.jax.org/staff/
lindsay_shopland.html
Lab Members:
Megan McOsker, Research Assistant
Research:
Chromosome Structure and Function Within the Nucleus
Coordinated expression of multiple genes takes place within a three-dimensional, structural context, the nuclear chromosome territory. Both higher-order chromatin structure and the positioning of genes along the primary sequence are linked to gene expression, suggesting that these two levels of genome organization are functionally connected. Yet how the DNA fiber is successively packaged into a gene-expressing 3-D chromosome remains a fundamental, unanswered question. The goal of the Shopland laboratory is to provide answers to this question, testing 3-D structure-function relationships within the chromosome and using primary sequence and functional genomic annotation as a guide.
Our current experimental focus is a 10 Mb region of mouse Chromosome 14 that is genetically defined by the piebald deletion complex. We use cytological methods and high-resolution fluorescence microscopy to simultaneously probe multiple, specific sequences within this region, thereby gaining insight into complex 3-D relationships of different genomic elements. In collaboration with Dr. Christoph Cremer (IMB and University of Heidelberg), we are quantitatively defining and computationally modeling this large portion of chromosome 14, which represents ~ 1/10 of the chromosome. In addition, we are collaborating with Dr. Carol Bult (The Jackson Laboratory) and Dr. Tim O’Brien (Cornell University) to further define genomic features of this region that are critical for 3-D structure and gene expression. Plans are underway to examine chromosome structures at the highest resolution possible by light microscopy, using the IMB’s new 4Pi confocal laser scanning fluorescence microscope.
Recent Publications:
Shopland LS, Lawrence JB. 2000. Seeking common ground in nuclear complexity. J Cell Biol 150(1): F1-F4
Shopland LS, Byron M, Stein JL, Lian JB, Stein GS, Lawrence JB. 2001. Replication-dependent histone gene expression is related to Cajal body (CB) association but does not require sustained CB contact. Mol Biol Cell 12:565-576
Shopland LS, Johnson CV, Lawrence JB. 2002. Evidence that all SC-35 domains contain mRNAs and that transcripts can be structurally constrained within these domains. J Struct Biol 140:131-139
Tam R, Shopland LS, Johnson CV, McNeil J, Lawrence JB. 2002. Visualizing RNA transcription and splicing from individual genes. FISH: A Practical Approach Oxford University Press 260:93-118
Shopland LS, Johnson CV, Byron M, McNeil J, Lawrence JB. 2003. Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: Evidence for local euchromatic neighborhoods. J Cell Biol, 162:981-990
Moen PT, Johnson CV, Byron M, Shopland LS, de la Serna I, Imbalzano A, Lawrence JB. 2004. Repositioning of muscle-specific genes to the periphery of SC-35 domains during skeletal myogenesis. Mol Biol Cell 15:197-206
Shopland LS, Peterson K, Lynch CR, Thornton K, Kepper N, Stein S, Vincent S, Molloy KR, Kreth G, Cremer C, Bult CJ, O’Brien TP. 2005. Gene distribution pattern in the primary sequence defines higher-order chromatin structures. J Cell Biol (submitted)
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