Journal article
Transcriptional Dysregulation in NIPBL and Cohesin Mutant Human Cells
PLoS biology, v 7(5), pp e1000119-e1000119
01 May 2009
PMID: 19468298
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cohesin regulates sister chromatid cohesion during the mitotic cell cycle with Nipped-B-Like (NIPBL) facilitating its loading and unloading. In addition to this canonical role, cohesin has also been demonstrated to play a critical role in regulation of gene expression in nondividing cells. Heterozygous mutations in the cohesin regulator NIPBL or cohesin structural components SMC1A and SMC3 result in the multisystem developmental disorder Cornelia de Lange Syndrome (CdLS). Genome-wide assessment of transcription in 16 mutant cell lines from severely affected CdLS probands has identified a unique profile of dysregulated gene expression that was validated in an additional 101 samples and correlates with phenotypic severity. This profile could serve as a diagnostic and classification tool. Cohesin binding analysis demonstrates a preference for intergenic regions suggesting a cis-regulatory function mimicking that of a boundary/insulator interacting protein. However, the binding sites are enriched within the promoter regions of the dysregulated genes and are significantly decreased in CdLS proband, indicating an alternative role of cohesin as a transcription factor.
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Details
- Title
- Transcriptional Dysregulation in NIPBL and Cohesin Mutant Human Cells
- Creators
- Jinglan Liu - Children's Hospital of PhiladelphiaZhe Zhang - Children's Hospital of PhiladelphiaMasashige Bando - Tokyo Institute of TechnologyTakehiko Itoh - Tokyo Institute of TechnologyMatthew A. Deardorff - University of PennsylvaniaDinah Clark - Children's Hospital of PhiladelphiaManinder Kaur - Children's Hospital of PhiladelphiaStephany Tandy - Children's Hospital of PhiladelphiaTatsuro Kondoh - College Station Medical CenterEric Rappaport - Children's Hospital of PhiladelphiaNancy B. Spinner - Children's Hospital of PhiladelphiaHugo Vega - Universidad Nacional de ColombiaLaird G. Jackson - Drexel UniversityKatsuhiko Shirahige - Tokyo Institute of TechnologyIan D. Krantz - Children's Hospital of Philadelphia
- Publication Details
- PLoS biology, v 7(5), pp e1000119-e1000119
- Publisher
- Public Library Science
- Number of pages
- 16
- Grant note
- P01HD052860 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Pennsylvania Department of Health MEXT, Japan; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) PO1 HD052860; KO8 HD055488 / NICHD; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) K08HD055488 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) IDK CdLS Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000267282000015
- Scopus ID
- 2-s2.0-66249144416
- Other Identifier
- 991019350666704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biology