Next Article in Journal / Special Issue
New Frontiers in Melanoma Epigenetics—The More We Know, the More We Don’t Know
Previous Article in Journal
Welcome to the New Journal Epigenomes
Article Menu

Export Article

Open AccessArticle
Epigenomes 2017, 1(1), 2; doi:10.3390/epigenomes1010002

Helicase Lymphoid-Specific Enzyme Contributes to the Maintenance of Methylation of SST1 Pericentromeric Repeats That Are Frequently Demethylated in Colon Cancer and Associate with Genomic Damage

1
Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
2
Active Motif, 1914 Palomar Oaks Way, Suite 150, Carlsbad, CA 92008, USA
3
Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Campus Can Ruti, Badalona 08916, Barcelona, Spain
4
Departament de Ciències Fisiològiques, Facultat de Medicina i Ciències de la Salut, Campus Ciències de la Salut, Bellvitge, Universitat de Barcelona, Hospitalet del Llobregat 08907, Barcelona, Spain
5
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: Ernesto Guccione
Received: 27 July 2016 / Revised: 8 September 2016 / Accepted: 14 September 2016 / Published: 22 September 2016
(This article belongs to the Special Issue Biological Methylation in Development and Cancer)
View Full-Text   |   Download PDF [2816 KB, uploaded 26 December 2016]   |  

Abstract

DNA hypomethylation at repetitive elements accounts for the genome-wide DNA hypomethylation common in cancer, including colorectal cancer (CRC). We identified a pericentromeric repeat element called SST1 frequently hypomethylated (>5% demethylation compared with matched normal tissue) in several cancers, including 28 of 128 (22%) CRCs. SST1 somatic demethylation associated with genome damage, especially in tumors with wild-type TP53. Seven percent of the 128 CRCs exhibited a higher (“severe”) level of demethylation (≥10%) that co-occurred with TP53 mutations. SST1 demethylation correlated with distinct histone marks in CRC cell lines and primary tumors: demethylated SST1 associated with high levels of the repressive histone 3 lysine 27 trimethylation (H3K27me3) mark and lower levels of histone 3 lysine 9 trimethylation (H3K9me3). Furthermore, induced demethylation of SST1 by 5-aza-dC led to increased H3K27me3 and reduced H3K9me3. Thus, in some CRCs, SST1 demethylation reflects an epigenetic reprogramming associated with changes in chromatin structure that may affect chromosomal integrity. The chromatin remodeler factor, the helicase lymphoid-specific (HELLS) enzyme, called the “epigenetic guardian of repetitive elements”, interacted with SST1 as shown by chromatin immunoprecipitation, and down-regulation of HELLS by shRNA resulted in demethylation of SST1 in vitro. Altogether these results suggest that HELLS contributes to SST1 methylation maintenance. Alterations in HELLS recruitment and function could contribute to the somatic demethylation of SST1 repeat elements undergone before and/or during CRC pathogenesis. View Full-Text
Keywords: DNA demethylation; epigenetics; satellite element; colorectal cancer DNA demethylation; epigenetics; satellite element; colorectal cancer
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Samuelsson, J.K.; Dumbovic, G.; Polo, C.; Moreta, C.; Alibés, A.; Ruiz-Larroya, T.; Giménez-Bonafé, P.; Alonso, S.; Forcales, S.-V.; Perucho, M. Helicase Lymphoid-Specific Enzyme Contributes to the Maintenance of Methylation of SST1 Pericentromeric Repeats That Are Frequently Demethylated in Colon Cancer and Associate with Genomic Damage. Epigenomes 2017, 1, 2.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Epigenomes EISSN 2075-4655 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top