UMMS Affiliation

Department of Cell and Developmental Biology; Department of Pathology; Department of Neurology; Department of Medicine; Lawrence Lab

Publication Date


Document Type



Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Genetics and Genomics


This study reveals that high-copy satellite II (HSATII) sequences in the human genome can bind and impact distribution of chromatin regulatory proteins and that this goes awry in cancer. In many cancers, master regulatory proteins form two types of cancer-specific nuclear bodies, caused by locus-specific deregulation of HSATII. DNA demethylation at the 1q12 mega-satellite, common in cancer, causes PRC1 aggregation into prominent Cancer-Associated Polycomb (CAP) bodies. These loci remain silent, whereas HSATII loci with reduced PRC1 become derepressed, reflecting imbalanced distribution of UbH2A on these and other PcG-regulated loci. Large nuclear foci of HSATII RNA form and sequester copious MeCP2 into Cancer-Associated Satellite Transcript (CAST) bodies. Hence, HSATII DNA and RNA have an exceptional capacity to act as molecular sponges and sequester chromatin regulatory proteins into abnormal nuclear bodies in cancer. The compartmentalization of regulatory proteins within nuclear structure, triggered by demethylation of "junk" repeats, raises the possibility that this contributes to further compromise of the epigenome and neoplastic progression.


DNA methylation, breast cancer, cancer biomarkers, cancer epigenetics, centromere, nuclear structure, polycomb proteins, satellite heterochromatin

Rights and Permissions

Copyright 2017 The Author(s).

DOI of Published Version



Cell Rep. 2017 Mar 21;18(12):2943-2956. doi: 10.1016/j.celrep.2017.02.072. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.