Bivalent Epigenetic Control of Oncofetal Gene Expression in Cancer

Sayyed K Zaidi; Seth E Frietze; Jonathan A Gordon; Jessica L Heath; Terri Messier; Deli Hong; Joseph R Boyd; Mingu Kang; Anthony N Imbalzano; Jane B Lian; Janet L Stein; Gary S Stein

doi:10.1128/MCB.00352-17

Bivalent Epigenetic Control of Oncofetal Gene Expression in Cancer

Mol Cell Biol. 2017 Nov 13;37(23):e00352-17. doi: 10.1128/MCB.00352-17. Print 2017 Dec 1.

Authors

Sayyed K Zaidi^{1

2}, Seth E Frietze^{3

2}, Jonathan A Gordon^{1

2}, Jessica L Heath^{1

4

2}, Terri Messier^{1

2}, Deli Hong^{1

5}, Joseph R Boyd¹, Mingu Kang¹, Anthony N Imbalzano⁶, Jane B Lian^{1

2}, Janet L Stein^{1

2}, Gary S Stein^{7

2}

Affiliations

¹ Department of Biochemistry, University of Vermont, Burlington, Vermont, USA.
² University of Vermont Cancer Center, University of Vermont, Burlington, Vermont, USA.
³ Department of Medical Laboratory and Radiation Sciences, University of Vermont, Burlington, Vermont, USA.
⁴ Department of Pediatrics, University of Vermont, Burlington, Vermont, USA.
⁵ Graduate Program in Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
⁶ Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
⁷ Department of Biochemistry, University of Vermont, Burlington, Vermont, USA gary.stein@med.uvm.edu.

Abstract

Multiple mechanisms of epigenetic control that include DNA methylation, histone modification, noncoding RNAs, and mitotic gene bookmarking play pivotal roles in stringent gene regulation during lineage commitment and maintenance. Experimental evidence indicates that bivalent chromatin domains, i.e., genome regions that are marked by both H3K4me3 (activating) and H3K27me3 (repressive) histone modifications, are a key property of pluripotent stem cells. Bivalency of developmental genes during the G₁ phase of the pluripotent stem cell cycle contributes to cell fate decisions. Recently, some cancer types have been shown to exhibit partial recapitulation of bivalent chromatin modifications that are lost along with pluripotency, suggesting a mechanism by which cancer cells reacquire properties that are characteristic of undifferentiated, multipotent cells. This bivalent epigenetic control of oncofetal gene expression in cancer cells may offer novel insights into the onset and progression of cancer and may provide specific and selective options for diagnosis as well as for therapeutic intervention.

Keywords: bivalency; cancer; epigenetic control; nuclear structure; oncofetal gene expression.

Publication types

Review

MeSH terms

Animals
Cell Differentiation / genetics*
Chromatin / metabolism*
DNA Methylation / genetics
Gene Expression Regulation, Developmental / genetics*
Gene Expression Regulation, Neoplastic / genetics*
Histones / genetics
Histones / metabolism
Humans

Substances

Chromatin
Histones

Abstract

Publication types

MeSH terms

Substances

Grants and funding