UMMS Affiliation

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

Publication Date

3-21-2017

Document Type

Article

Disciplines

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

Abstract

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.

Rights and Permissions

Copyright 2017 The Author(s).

DOI of Published Version

10.1016/j.celrep.2017.02.072

Source

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

Related Resources

Link to Article in PubMed

Keywords

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

Journal/Book/Conference Title

Cell reports

PubMed ID

28329686

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.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.