دانلود رایگان مقاله تنظیم اپی ژنتیک میوژنز جنینی و بازسازی عضلات با اصلاح متیلاسیون

Abstract

Skeletal muscle formation in vertebrates is derived from the paraxial mesoderm, which develops into myogenic precursor cells and finally differentiates into mature myofibers. This myogenic program involves temporal-spatial molecular events performed by transcription regulators (such as members of the Pax, MRFs and Six families) and signaling pathways (such as Wnts, BMP and Shh signaling). Epigenetic regulation, including histone post-translational modifications is crucial for controlling gene expression through recruitment of various chromatin-modifying enzymes that alter chromatin dynamics during myogenesis. The chromatin modifying enzymes are also recruited at regions of muscle gene regulation, coordinating transcription regulators to influence gene expression. In particular, the reversible methylation status of histone N-terminal tails provides the important regulatory mechanisms in either activation or repression of muscle genes. In this report, we review the recent literatures to deduce mechanisms underlying the epigenetic regulation of gene expression with a focus on histone methylation modification during embryo myogenesis and adult muscle regeneration. Recent results from different histone methylation/demethylation modifications have increased our understanding about the highly intricate layers of epigenetic regulations involved in myogenesis and cross-talk of histone enzymes with the muscle-specific transcriptional machinery.

4. Conclusions

Chromatin modifiers mediate dynamic modifications of histone tails that are vital to reprogramming cells toward terminal differentiation. Genetic and epigenetic mechanisms ensure that complex developmental programs are correctly executed [83]. In this report, we review the recent literature to deduce mechanisms underlying a complex interplay between myogenic regulatory factors and histone methylation modifications and reveal the reciprocal regulation between histone methyltransferases and demethyltransferases in the control of gene expression during skeletal muscle myogenesis and regeneration (Fig. 3). We also elucidate that histone chaperones play critical roles in controlling of muscle gene regulatory programs in this review. In addition, we find that histone methyltransferases not only mediate dynamic modifications of histone tails for influencing myogenic gene expression during skeletal myogenesis but also catalyze myogenic regulatory factors methylation at lysine site in controlling of gene transcription activity. To date, little is known about the role of histone methylation modifications in adult muscle regeneration. However, a similar regulatory mechanism from myogenesis might regulate the availability and composition of chromatin modifyingcomplexes that promote muscle gene transcription in adult muscle regeneration. Likewise, we predict that histone methylationmodifying enzymes mediate dynamic modifications of histone tails that are vital to programming myogenic precursors (satellite cells) toward terminal differentiation in adult muscle regeneration.