Spatial chromatin organization is crucial for transcriptional regulation and might be particularly important in neurons since they dramatically change their transcriptome in response to external stimuli. We show that stimulation of neurons causes condensation of large chromatin domains. This phenomenon can be observed in vitro in cultured rat hippocampal neurons as well as in vivo in the amygdala and hippocampal neurons. Activity-induced chromatin condensation is an active, rapid, energy-dependent, and reversible process. It involves calcium-dependent pathways but is independent of active transcription. It is accompanied by the redistribution of posttranslational histone modifications and rearrangements in the spatial organization of chromosome territories. Moreover, it leads to the reorganization of nuclear speckles and active domains located in their proximity. Finally, we find that the histone deacetylase HDAC1 is the key regulator of this process. Our results suggest that HDAC1-dependent chromatin reorganization constitutes an important level of transcriptional regulation in neurons.
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http://dx.doi.org/10.1016/j.celrep.2022.110352 | DOI Listing |
DNA (Basel)
March 2024
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Embryogenesis is characterized by dynamic chromatin remodeling and broad changes in chromosome architecture. These changes in chromatin organization are accompanied by transcriptional changes, which are crucial for the proper development of the embryo. Several independent mechanisms regulate this process of chromatin reorganization, including segregation of chromatin into heterochromatin and euchromatin, deposition of active and repressive histone modifications, and the formation of 3D chromatin domains such as TADs and LADs.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Faculty of Biology, Lomonosov Moscow State University, Moscow, 119991 Russia.
The functions of actin and its motor proteins myosins in the cytoplasm have been the subject of research for more than 100 years, but the existence and function of these proteins in the nucleus has been a matter of debate until recently. Recent data has clarified the role of actin and myosin molecules in controlling the dynamics of processes in the cell nucleus, chromatin organization and genome integrity. New microscopy techniques and the use of modified actin-binding probes have made it possible for the first time to directly visualize the polymerization of actin filaments in the nucleus of living cells.
View Article and Find Full Text PDFJ Dent Res
December 2024
Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Head and neck squamous cell carcinoma (HNSCC) is one of the deadliest human cancers, with the overall 5-year survival rate stagnating in recent decades due to the lack of innovative treatment approaches. Apart from the recently Food and Drug Administration-approved epidermal growth factor receptor inhibitor and immune checkpoint inhibitor, alternative therapeutic strategies that target epigenetic abnormalities, an emerging cancer hallmark, remain to be fully explored. A pathological epigenetic landscape, characterized by widespread reprogramming of chromatin modifications such as DNA methylation and histone modifications, which drives transcription deregulation and genome reorganization, has been extensively documented in numerous cancers, including HNSCC.
View Article and Find Full Text PDFGenome Biol Evol
December 2024
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, Guangdong, China.
Protamines (PRMs) and transition nuclear proteins (TNPs) are two key classes of sperm nuclear basic proteins that regulate chromatin reorganization and condensation in the spermatozoon head, playing crucial roles in mammalian spermatogenesis. In scrotal mammals, such as humans, cryptorchidism, the failure of the testes to descend into the scrotal sac is generally associated with higher rates of defective spermatozoon quality and function. However, ascrotal mammals, such as cetaceans, with naturally undescended testes, produce normal spermatozoa similar to their scrotal counterparts.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Kirchhoff-Institute for Physics, Heidelberg University, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany.
In radiation tumor therapy, irradiation, on one hand, should cause cell death to the tumor. On the other hand, the surrounding non-tumor tissue should be maintained unaffected. Therefore, methods of local dose enhancements are highly interesting.
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