Histone acetylation and chromatin signature in stem cell identity and cancer.
Cancers are traditionally viewed as a primarily genetic disorder, however this view has recently been modified by compelling evidence arguing that epigenetic events play important roles in most human cancers. Deregulation of epigenetic information (encoded in DNA methylation and histone modification patterns) in cells with pluripotent potential may alter defining properties of stem cells, self-renewal and differentiation potential, leading to cancer initiation and progression. The level of compaction of chromatin dictates accessibility to genomic DNA and therefore has a key role in establishing and maintaining distinct gene expression patterns and consequently pluripotent state and differentiation fates of stem cells. Unique properties of stem cells defined as "stemness" may be determined by acetylation and methylation of histones near gene promoters that regulate gene transcription, however these histone modifications elsewhere in the genome may also be important. In this review, we discuss new insights into possible mechanisms by which histone acetyltransferases (HATs) and histone acetylation in concert with other chromatin modifications may regulate pluripotency, and speculate how deregulation of histone marking may lead to tumourigenesis.
Shukla
Vivek
V
International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
Vaissière
Thomas
T
Herceg
Zdenko
Z
D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D039904:Pluripotent Stem Cells / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D013234:Stem Cells / Q000502:physiology*
D002843:Chromatin; D006657:Histones; D051548:Histone Acetyltransferases