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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

Linking mitochondria metabolism, developmental timing, and human brain evolution
Curr Opin Genet Dev. 2024 Mar 30;86:102182. doi: 10.1016/j.gde.2024.102182. Online ahead of print.ABSTRACTChanges in developmental timing are an important factor of evolution in organ shape and function. This is particularly striking for human brain development, which, compared with other mammals, is considerably prolonged at the level of the cerebral cortex, resulting in brain neoteny. Here, we review recent findings that indicate that mitochondria and metabolism contribute to species differences in the tempo of cortical neuron development. Mitochondria display species-specific developmental timeline and metabolic activit...
Source: Current Opinion in Genetics and Development - March 31, 2024 Category: Genetics & Stem Cells Authors: Pierre Casimir Ryohei Iwata Pierre Vanderhaeghen Source Type: research