Long-term effects of chromatin remodeling and DNA damage in stem cells induced by environmental and dietary agents

Abstract

The presence of histones acts as a barrier to protein access; thus chromatin remodeling must occur for essential processes such as transcription and replication. In conjunction with histone modifications, DNA methylation plays critical roles in gene silencing through chromatin remodeling. Chromatin remodeling is also interconnected with the DNA damage response, maintenance of stem cell properties, and cell differentiation programs. Chromatin modifications have increasingly been shown to produce long-lasting alterations in chromatin structure and transcription. Recent studies have shown environmental exposures in utero have the potential to alter normal developmental signaling networks, physiologic responses, and disease susceptibility later in life during a process known as developmental reprogramming. In this review we discuss the long-term impact of exposure to environmental compounds, the chromatin modifications that they induce, and the differentiation and developmental programs of multiple stem and progenitor cell types altered by exposure. The main focus is to highlight agents present in the human lifestyle that have the potential to promote epigenetic changes that impact developmental programs of specific cell types, may promote tumorigenesis through altering epigenetic marks, and may be transgenerational, for example, those able to be transmitted through multiple cell divisions.

FIG. 1

Environmental toxins. The chemical structure and biologic consequences of aldehydes and alcohols as well as benzene and its metabolites are shown.

FIG. 2

Environmental toxins: trace metals. The biologic consequences of exposure to trace metals are shown.

FIG. 3

Estrogenic compounds: dietary exposures and supplements. The chemical structure and biologic consequences of xenoestrogens as well as phytoestrogens and bioflavonoids are shown. Of note is the similar phenolic ring structure of phytoestrogen and bioflavonoid compounds to etoposide, a potent inhibitor of topoII.