Reflections and perspectives on epigenetically mediated biological control: compromises in cancer and skeletal pathology

Establishing DNA as the genetic material, deciphering the genetic code and defining the double helical structure of the genome provided a foundation for pursuing a mechanistic understanding of gene expression that is operative for biological control and pathology. Equally important are a series of discoveries that have established epigenetic mechanisms, defined as the control of gene expression by non-DNA-encoded regulation, mediated by an evolving histone code that supports chromatin states, as complementary and obligatory determinants for biological activity. Evidence is accruing for pivotal contributions by epigenetic parameters of control to gene expression that is required for development and differentiation as well as for transient and sustained responsiveness to physiological regulatory cues that support cell structure, function, cell survival, tissue repair and remodeling. Epigenetic control is emerging as a decisive contributor to the regulatory compliance for the highly integrative processes that balance phenotypic function and tumor suppression with aberrant gene expression that accompanies the onset and progression of disease, strikingly illustrated with tumorigenesis and skeletal disorders.