RESUMEN
Metazoan development arises from spatiotemporal control of gene expression, which depends on epigenetic regulators like the polycomb group proteins (PcG) that govern the chromatin landscape. PcG proteins facilitate the addition and removal of histone 2A monoubiquitination at lysine 119 (H2AK119ub1), which regulates gene expression, cell fate decisions, cell cycle progression, and DNA damage repair. Regulation of these processes by PcG proteins is necessary for proper development, as pathogenic variants in these genes are increasingly recognized to underly developmental disorders. Overlapping features of developmental syndromes associated with pathogenic variants in specific PcG genes suggest disruption of central developmental mechanisms; however, unique clinical features observed in each syndrome suggest additional non-redundant functions for each PcG gene. In this review, we describe the clinical manifestations of pathogenic PcG gene variants, review what is known about the molecular functions of these gene products during development, and interpret the clinical data to summarize the current evidence toward an understanding of the genetic and molecular mechanism.
RESUMEN
Generating needed cell types using cellular reprogramming is a promising strategy for restoring tissue function in injury or disease. A common method for reprogramming is addition of one or more transcription factors that confer a new function or identity. Advancements in transcription factor selection and delivery have culminated in successful grafting of autologous reprogrammed cells, an early demonstration of their clinical utility. Though cellular reprogramming has been successful in a number of settings, identification of appropriate transcription factors for a particular transformation has been challenging. Computational methods enable more sophisticated prediction of relevant transcription factors for reprogramming by leveraging gene expression data of initial and target cell types, and are built on mathematical frameworks ranging from information theory to control theory. This review highlights the utility and impact of these mathematical frameworks in the field of cellular reprogramming. This article is categorized under: Reproductive System Diseases > Reproductive System Diseases>Genetics/Genomics/Epigenetics Reproductive System Diseases > Reproductive System Diseases>Stem Cells and Development Reproductive System Diseases > Reproductive System Diseases>Computational Models.