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ROCKVILLE, MD, United States

Wesolowska N.,U.S. National Institutes of Health | Wesolowska N.,Johns Hopkins University | Amariei F.L.,U.S. National Institutes of Health | Amariei F.L.,Origene Technologies, Inc. | Rong Y.S.,U.S. National Institutes of Health
Genetics | Year: 2013

Telomeres are obligatory chromosomal landmarks that demarcate the ends of linear chromosomes to distinguish them from broken ends and can also serve to organize the genome. In both budding and fission yeast, they cluster at the periphery of the nucleus, potentially to establish a compartment of silent chromatin. To gain insight into telomere organization in higher organisms, we investigated their distribution in interphase nuclei of Drosophila melanogaster. We focused on the syncytial blastoderm, an excellent developmental stage for live imaging due to the synchronous division of the nuclei at this time. We followed the EGFP-labeled telomeric protein HOAP in vivo and found that the 16 telomeres yield four to six foci per nucleus, indicative of clustering. Furthermore, we confirmed clustering in other somatic tissues. Importantly, we observed that HOAP signal intensity in the clusters increases in interphase, potentially due to loading of HOAP to newly replicated telomeres. To determine the rules governing clustering, we used in vivo imaging and fluorescence in situ hybridization to test several predictions. First, we inspected mutant embryos that develop as haploids and found that clustering is not mediated by associations between homologs. Second, we probed specifically for a telomere of novel sequence and found strong evidence against DNA sequence identity and homology as critical factors. Third, we ruled out predominance of intrachromosomal interactions by marking both ends of a chromosome. Based on these results, we propose that clustering is independent of sequence and is likely maintained by an as yet undetermined factor. © 2013 by the Genetics Society of America. Source


Lee M.-H.,U.S. National Institutes of Health | Lahusen T.,U.S. National Institutes of Health | Wang R.-H.,U.S. National Institutes of Health | Xiao C.,U.S. National Institutes of Health | And 5 more authors.
Oncogene | Year: 2012

Expression of the breast cancer-associated gene 1 (BRCA1) in sporadic breast cancers is usually reduced, yet the underlying mechanisms remains elusive. To identify factors that are responsible for reduced BRCA1 expression, we screened 92 known transcription factors for their ability to regulate expression of BRCA1. Among several potential regulators, the Gli-Krueppel-related transcription factor Yin Yang 1 (YY1) showed the most dramatic transactivation of the BRCA1 promoter. YY1 binds to the promoter of BRCA1, and its overexpression resulted in increased expression of BRCA1 and a number of BRCA1 downstream genes. We further showed that overexpression of YY1 in cancer cells inhibited cell proliferation, foci formation and tumor growth in nude mice. To assess the clinical relevance between YY1 and BRCA1, we studied expression of YY1 and BRCA1 from human breast cancer samples and tissue arrays, and detected a significant positive correlation between the level of YY1 and BRCA1 expression in these cancers. Taken together, these findings suggest that YY1 is a key regulator of BRCA1 expression and may be causally linked to the molecular etiology of human breast cancer. © 2012 Macmillan Publishers Limited All rights reserved. Source


Patent
Origene Technologies, Inc. | Date: 2010-09-23

Illustrative embodiments herein disclosed relate to protein arrays, methods for making the arrays and methods for using them, among others. In some embodiments known proteins representing at least 50% of the loci in the human genome are arrayed in known positions on a support. In some embodiments arrays are made of proteins purified from cell lysates by affinity binding to the support. In some embodiments protein arrays are used to decode the binding specificity of antibodies. In some embodiments protein arrays are used to diagnose auto-immune disorders. Many other embodiments and general features are disclosed.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 217.93K | Year: 2004

DESCRIPTION (provided by applicant): The latest build of human genome "build 34" contains 21,335 unique reference sequences that represent 17,869 unique loci. A survey of the open reading frame (ORF) size reveals that 635 reference sequences contain O


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.00M | Year: 2015

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