We have mapped CENPA genome wide in 4 colorectal cancer cell lines and found that instead of being broadly mis-localized as was originally hypothesized, our preliminary findings suggest that it is clustered tightly within a 1000bp windown in very specific locations. These locations appear to areas of the genome that are enriched in genes, area of the genome that contain regulatory regions,and areas of the genome that may potentially represent breakpoints in subtelomeres. Furthermore, we find that some sites of enrichment are common across two cancer cell lines that have the highest levels of misexpression of the CENPA protein, suggesting a common mechanism may underlie how CENPA invades non-centromeric locations in the genome. We intend to map these regions further using cytological and single molecule microscopy (AFM) methods.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011206-01
Application #
7966216
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2009
Total Cost
$529,614
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Nye, Jonathan; Melters, Daniël P; Dalal, Yamini (2018) The Art of War: harnessing the epigenome against cancer. F1000Res 7:141
Nuccio, A G; Bui, M; Dalal, Y et al. (2017) Mass Spectrometry-Based Methodology for Identification of Native Histone Variant Modifications From Mammalian Tissues and Solid Tumors. Methods Enzymol 586:275-290
Melters, Daniël P; Nye, Jonathan; Zhao, Haiqing et al. (2015) Chromatin Dynamics in Vivo: A Game of Musical Chairs. Genes (Basel) 6:751-76
Quénet, Delphine; Dalal, Yamini (2012) The CENP-A nucleosome: a dynamic structure and role at the centromere. Chromosome Res 20:465-79