Epigenetic histone modifications and master regulators as determinants of context dependent nuclear receptor activity in bone cells

Bone. 2015 Dec:81:757-764. doi: 10.1016/j.bone.2015.03.012. Epub 2015 Mar 27.

Abstract

Genomic annotation of unique and combinatorial epigenetic modifications along with transcription factor occupancy is having a profound impact on our understanding of the genome. These studies have led to a better appreciation of the dynamic nature of the epigenetic and transcription factor binding components that reveal overarching principles of the genome as well as tissue specificity. In this minireview, we discuss the presence and potential functions of several of these features across the genome in osteoblast lineage cells. We examine how these features are modulated during cellular maturation, affect transcriptional output and phenotype, and how they alter the ability of cells to respond to systemic signals directed by calcemic hormones such as 1,25-dihydroxyvitamin D3 and PTH. In particular, we describe recent experiments which indicate that progressive stages of bone cell differentiation affect RUNX2 binding to the genome, modify and restrict patterns of gene expression, and dramatically alter cellular response to the vitamin D hormone. These studies expand our understanding of mechanisms that govern steroid hormone regulation of gene expression, while highlighting the increasing complexity that is evident relative to these basic cellular processes. The results also have profound implications with respect to the impact of skeletal diseases on transcriptional outcomes as well. This article is part of a Special Issue entitled Epigenetics and Bone.

Keywords: Epigenetics; Genome-wide analysis; Osteoblast lineage cells; Transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bone and Bones / cytology*
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Calcitriol / pharmacology
  • Cell Differentiation / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Epigenesis, Genetic*
  • Histone Code / genetics*
  • Humans
  • Models, Biological
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Parathyroid Hormone / pharmacology
  • Receptors, Calcitriol / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Core Binding Factor Alpha 1 Subunit
  • Parathyroid Hormone
  • Receptors, Calcitriol
  • Receptors, Cytoplasmic and Nuclear
  • Calcitriol