The long term goal of the investigator is to understand the functional organization of the cell nucleus and how the processes of transcription, pre-mRNA splicing, and RNA transport are coordinated in the living cell. The short term goals are to determine the spatial organization of RNA polymerase II transcription and pre-mRNA splicing in mammalian cell nuclei. Specific studies will be aimed at determining the dynamics of splicing factors in living cells and in identifying signals involved in the movement of factors from storage and/or reassembly sites to regions of active transcription. To biochemically characterize nuclear substructures believed to be involved in splicing factor storage and/or reassembly, interchromatin granule clusters will be purified and used to obtain monoclonal antibodies. Electron microscopy in situ hybridization will be used to track the movement of several endogenous mRNAs from their sites of synthesis to the nuclear envelope. This work will serve as a framework for the examination of cells or tissues associated with various disease states with the potential for developing phenotypic screens for susceptibility and/or diagnosis of abnormalities.
| Arun, Gayatri; Diermeier, Sarah D; Spector, David L (2018) Therapeutic Targeting of Long Non-Coding RNAs in Cancer. Trends Mol Med 24:257-277 |
| Zhang, Bin; Mao, Yuntao S; Diermeier, Sarah D et al. (2017) Identification and Characterization of a Class of MALAT1-like Genomic Loci. Cell Rep 19:1723-1738 |
| Bergmann, Jan H; Li, Jingjing; Eckersley-Maslin, Mélanie A et al. (2015) Regulation of the ESC transcriptome by nuclear long noncoding RNAs. Genome Res 25:1336-46 |
| Zepeda-Mendoza, Cinthya J; Mukhopadhyay, Swagatam; Wong, Emily S et al. (2015) Quantitative analysis of chromatin interaction changes upon a 4.3 Mb deletion at mouse 4E2. BMC Genomics 16:982 |
| Hogan, Megan S; Parfitt, David-Emlyn; Zepeda-Mendoza, Cinthya J et al. (2015) Transient pairing of homologous Oct4 alleles accompanies the onset of embryonic stem cell differentiation. Cell Stem Cell 16:275-88 |
| Bergmann, Jan H; Spector, David L (2014) Long non-coding RNAs: modulators of nuclear structure and function. Curr Opin Cell Biol 26:10-8 |
| Eckersley-Maslin, Mélanie A; Spector, David L (2014) Random monoallelic expression: regulating gene expression one allele at a time. Trends Genet 30:237-44 |
| Eckersley-Maslin, Mélanie A; Thybert, David; Bergmann, Jan H et al. (2014) Random monoallelic gene expression increases upon embryonic stem cell differentiation. Dev Cell 28:351-65 |
| Shi, Junwei; Whyte, Warren A; Zepeda-Mendoza, Cinthya J et al. (2013) Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation. Genes Dev 27:2648-62 |
| Bodnar, Megan S; Spector, David L (2013) Chromatin meets its organizers. Cell 153:1187-9 |
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