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Timing mechanisms: insights from comparative neural differentiation systems
Curr Opin Genet Dev. 2024 Apr 21;86:102197. doi: 10.1016/j.gde.2024.102197. Online ahead of print.ABSTRACTTemporal control is central to deploy and coordinate genetic programs during development. At present, there is limited understanding of the molecular mechanisms that govern the duration and speed of developmental processes. Timing mechanisms may run in parallel and/or interact with each other to integrate temporal signals throughout the organism. In this piece, we consider findings on the extrinsic control of developmental tempo and discuss the intrinsic roles of cell cycle, metabolic rates, protein turnover, and post-...
Source: Current Opinion in Genetics and Development - April 22, 2024 Category: Genetics & Stem Cells Authors: Chiara Azzi Teresa Rayon Source Type: research

RNA editing and immune control: from mechanism to therapy
We describe how ADAR1 regulates various dsRNA innate immune receptors through distinct mechanisms. Furthermore, we discuss the implications of ADAR1 and RNA editing in diseases, including autoimmune diseases and cancers.PMID:38643591 | DOI:10.1016/j.gde.2024.102195 (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - April 21, 2024 Category: Genetics & Stem Cells Authors: Shi-Bin Hu Jin Billy Li Source Type: research

Attraction and disruption: how loop extrusion and compartmentalisation shape the nuclear genome
Curr Opin Genet Dev. 2024 Apr 17;86:102194. doi: 10.1016/j.gde.2024.102194. Online ahead of print.ABSTRACTChromatin loops, which bring two distal loci of the same chromosome into close physical proximity, are the ubiquitous units of the three-dimensional genome. Recent advances in understanding the spatial organisation of chromatin suggest that several distinct mechanisms control chromatin interactions, such as loop extrusion by cohesin complexes, compartmentalisation by phase separation, direct protein-protein interactions and others. Here, we review different types of chromatin loops and highlight the factors and process...
Source: Current Opinion in Genetics and Development - April 18, 2024 Category: Genetics & Stem Cells Authors: Mikhail Magnitov Elzo de Wit Source Type: research

Mechanistic drivers of chromatin organization into compartments
Curr Opin Genet Dev. 2024 Apr 15;86:102193. doi: 10.1016/j.gde.2024.102193. Online ahead of print.ABSTRACTThe human genome is not just a simple string of DNA, it is a complex and dynamic entity intricately folded within the cell's nucleus. This three-dimensional organization of chromatin, the combination of DNA and proteins in the nucleus, is crucial for many biological processes and has been prominently studied for its intricate relationship to gene expression. Indeed, the transcriptional machinery does not operate in isolation but interacts intimately with the folded chromatin structure. Techniques for chromatin conforma...
Source: Current Opinion in Genetics and Development - April 16, 2024 Category: Genetics & Stem Cells Authors: Hannah L Harris M Jordan Rowley Source Type: research

Epigenetic priming in the male germline
Curr Opin Genet Dev. 2024 Apr 11;86:102190. doi: 10.1016/j.gde.2024.102190. Online ahead of print.ABSTRACTEpigenetic priming presets chromatin states that allow the rapid induction of gene expression programs in response to differentiation cues. In the germline, it provides the blueprint for sexually dimorphic unidirectional differentiation. In this review, we focus on epigenetic priming in the mammalian male germline and discuss how cellular memories are regulated and inherited to the next generation. During spermatogenesis, epigenetic priming predetermines cellular memories that ensure the lifelong maintenance of spermat...
Source: Current Opinion in Genetics and Development - April 12, 2024 Category: Genetics & Stem Cells Authors: Yuka Kitamura Satoshi H Namekawa Source Type: research

New insights into how to induce and maintain embryonic diapause in the blastocyst
Curr Opin Genet Dev. 2024 Apr 10;86:102192. doi: 10.1016/j.gde.2024.102192. Online ahead of print.ABSTRACTEmbryonic diapause in mammals is a period of developmental pause of the embryo at the blastocyst stage. During diapause, the blastocyst has minimal cell proliferation, metabolic activity and gene expression. At reactivation, blastocyst development resumes, characterised by increases in cell number, biosynthesis and metabolism. Until recently, it has been unknown how diapause is maintained without any loss of blastocyst viability. This review focuses on recent progress in the identification of molecular pathways occurri...
Source: Current Opinion in Genetics and Development - April 11, 2024 Category: Genetics & Stem Cells Authors: Jane C Fenelon Source Type: research

Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia
Curr Opin Genet Dev. 2024 Apr 4;86:102191. doi: 10.1016/j.gde.2024.102191. Online ahead of print.ABSTRACTTo make a multicellular organism, genes need to be transcribed at the right developmental stages and in the right tissues. DNA sequences termed 'enhancers' are crucial to achieve this. Despite concerted efforts, the exact mechanisms of enhancer activity remain elusive. Mixed lineage leukemia (MLL or KMT2A) rearrangements (MLLr), commonly observed in cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia, produce novel in-frame fusion proteins. Recent work has shown that the MLL-AF4 fusion protein drives ...
Source: Current Opinion in Genetics and Development - April 5, 2024 Category: Genetics & Stem Cells Authors: Thomas A Milne Source Type: research

Therapeutic targeting of BET bromodomain and other epigenetic acetylrecognition domain-containing factors
In conclusion, the potential for further development is discussed with a focus on proximity-based therapies targeting this class of epigenetic factors.PMID:38564841 | DOI:10.1016/j.gde.2024.102181 (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - April 2, 2024 Category: Genetics & Stem Cells Authors: Sarah Gold Ali Shilatifard Source Type: research