M S-medecine Sciences最新文献

The memory of cellular identity is crucial for the correct development of an individual and is maintained throughout life by the epigenome. Chromatin marks, such as DNA methylation and histone modifications, ensure the stability of gene expression programmes over time and through cell division. Loss of these marks can lead to severe pathologies, including cancer and developmental syndromes. However, reprogramming of cellular identity is also a natural phenomenon that occurs early in mammalian development, particularly in the germ line, which enables the production of mature and functional gametes. The germ line transmits genetic and epigenetic information to the next generation, contributing to the survival of the species. Primordial germ cells (PGCs) undergo extensive chromatin remodelling, including global DNA demethylation and erasure of the parental imprints. This review introduces the concept of epigenetic reprogramming, its discovery and key steps, as well as the transcriptional and chromatin changes that accompany germ cell formation in mice. Finally, we discuss the epigenetic mechanisms of genomic imprinting, its discovery, regulation and relevance to human disease.

Cellular differentiation and homeostasis rely on complex mechanisms to control gene expression, enabling the different cell lineages of an organism to establish and then "memorize" different epigenetic states. The processes that control gene expression are centered on chromatin, a complex of DNA, histone proteins and RNA, whose structure is finely regulated. Targeted epigenomic engineering tools make it possible to interfere with and study these processes, revealing the logic of epigenetic memory mechanisms. This article reviews the main classes of targeted epigenome modification tools and illustrates how they can be used to better understand and modify the epigenome of cells, paving the way for potentially revolutionary therapeutic prospects.

Alterations in DNA methylation profiles are typically found in cancer cells, combining genome-wide hypomethylation with hypermethylation of specific regions, such as CpG islands, which are normally unmethylated. Driving effects in cancer development have been associated with alteration of DNA methylation in certain regions, inducing, for example, the repression of tumor suppressor genes or the activation of oncogenes and retrotransposons. These alterations represent prime candidates for the development of specific markers for the detection, diagnosis and prognosis of cancer. In particular, these markers, distributed along the genome, provide a wealth of information that offers potential for innovation in the field of liquid biopsy, in particular thanks to the emergence of artificial intelligence for diagnostic purposes. This could overcome the limitations related to sensitivities and specificities, which remain too low for the most difficult applications in oncology: the detection of cancers at an early stage, the monitoring of residual disease and the analysis of brain tumors. In addition, targeting the enzymatic processes that control the epigenome offers new therapeutic strategies that could reverse the regulatory anomalies of these altered epigenomes.

What if the presence of two X chromosomes confers functional specificities on female cells and contributes to the different susceptibilites of men and women to certain diseases? One of the X chromosomes is randomly silenced in each female cell from the embryonic stage, theoretically making the sexes equal. This silencing of the X chromosome is a unique epigenetic process, affecting an entire chromosome and resulting in mosaic expression of X-linked genes throughout the body. However, some genes escape this process and X-inactivation appears to be somewhat labile in certain cell types. What are the physiological implications of these observations? This question is beginning to be explored, particularly in the immune and nervous systems, where several pathologies have sexual bias.