Our ultimate goal is to elucidate and understand the functional organization of the interphase nucleus and the interactions which occur between functional regions. Once functional domains become characterized they will provide a basis for more precisely evaluating cellular function and dysfunction. Thus far there has not been a direct mechanism for integrating DNA sequence information and genetic data into a coherent spatial picture of how genes function within the cell nucleus. Our studies are designed to establish a framework for evaluating the spatial organization of genes and their products throughout the cell cycle. The preferential localization of specific genes at specific interphase loci will have important implications for gene control and development. Our short term goal is to characterize where a specific gene is transcribed, where its message is processed and what path the message takes to exit the nucleus. Our initial studies will use in situ hybridization to evaluate the distribution of interphase genes based on the type of transcription unit, future studies will evaluate whether cell cycle regulated genes, housekeeping genes, structural genes or developmentally regulated genes localize clustered patterns in the interphase nucleus. Furthermore, we will evaluate the pathway of a pre-mRNA of an intron-containing gene and an intron-less gene to determine if there are unique or general pathways of nuclear message transport. If unique sites of gene localization can be identified and pathways of nuclear message transport described these data may be extremely useful for prenatal diagnosis and/or biopsy evaluation whereby it may be possible to identify changes in the 3-D spatial localization of a gene which may later manifest in the development of a pathological condition.
| 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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