Abstract
Within the eukaryotic nucleus the genomic DNA is organized into chromatin by stably interacting with the histone proteins as well as with several other nuclear components including non-histone proteins and non-coding RNAs. Together these interactions distribute the genetic material into chromatin subdomains which can exhibit higher and lower compaction levels. This organization contributes to differentially control the access to genomic sequences encoding key regulatory genetic information. In this context, epigenetic mechanisms play a critical role in the regulation of gene expression as they modify the degree of chromatin compaction to facilitate both activation and repression of transcription. Among the most studied epigenetic mechanisms we find the methylation of DNA, ATP-dependent chromatin remodeling, and enzyme-mediated deposition and elimination of post-translational modifications at histone and non-histone proteins. In this mini review, we discuss evidence that supports the role of these epigenetic mechanisms during transcriptional control of osteoblast-related genes. Special attention is dedicated to mechanisms of epigenetic control operating at the Runx2 and Sp7 genes coding for the two principal master regulators of the osteogenic lineage during mesenchymal stem cell commitment.
Highlights
Osteoblast lineage commitment is regulated by a coordinated set of extra cellular stimuli and developmentally-regulated signaling pathways, including those mediated by bone morphogenic proteins (BMPs), Wnt-ligands, steroid hormones, and growth factors, among others (Li et al, 1998; Nishimura et al, 1998; Drissi et al, 2000; Yamaguchi et al, 2000; Zhang et al, 2008)
Enrichment of H3K9me3/2 at transcriptionally-inactive chromatin can be associated with the presence of 5mCpG. This is due to the ability of the proteins that “write” and “read” these two epigenetic marks to form complexes (Janssen et al, 2018; Nicetto and Zaret, 2019) thereby providing a means for both repressive epigenetic modifications (5mCpG and H3K9me3) to collaborate in generating a condensed chromatin structure that reduces transcription. These findings further indicate that different epigenetic mechanisms leading to chromatin remodeling and transcriptional control can function in a coordinated and complementary manner within eukaryotic cells, allowing an effective regulation of gene expression in response to physiological cues
Future studies will need to consider the influence of the mechanical environments at which mesenchymal stem cells (MSCs) are maintained and differentiated ex vivo
Summary
Reviewed by: Quamarul Hassan, University of Alabama at Birmingham, United States Liliana Burlibasa, University of Bucharest, Romania. This organization contributes to differentially control the access to genomic sequences encoding key regulatory genetic information In this context, epigenetic mechanisms play a critical role in the regulation of gene expression as they modify the degree of chromatin compaction to facilitate both activation and repression of transcription. Among the most studied epigenetic mechanisms we find the methylation of DNA, ATP-dependent chromatin remodeling, and enzyme-mediated deposition and elimination of post-translational modifications at histone and non-histone proteins. In this mini review, we discuss evidence that supports the role of these epigenetic mechanisms during transcriptional control of osteoblast-related genes.
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