How h3k27me3 is regulated in progeria?5 answersH3K27me3 regulation plays a crucial role in various biological processes, including cancer, neuronal maturation, endometriosis, and pregnancy. In the context of progeria, the dynamic regulation of H3K27me3 is essential for proper differentiation and gene expression control. Dysregulation of H3K27me3 modifiers, such as EZH2 and Kdm6b, can lead to aberrant methylation patterns, impacting cellular plasticity and disease progression. Studies suggest that H3K27me3 levels are intricately linked to gene expression changes, with alterations in H3K27me3 occurring as a consequence rather than a trigger of transcriptional activity. Understanding the regulatory mechanisms of H3K27me3 in progeria could provide insights into disease pathogenesis and potential therapeutic targets.
Does histone H3.3 play a role in aging?6 answersHistone H3.3 plays a significant role in the aging process, as evidenced by various studies that have explored its impact on chromatin dynamics, gene expression, and cellular longevity. The accumulation of H3.3 in postmitotic cells with age suggests a pivotal role in modulating the chromatin landscape over an organism's lifespan. This accumulation is associated with profound changes in global levels of histone methyl modifications, indicating a causal relationship between H3 variant replacement and age-dependent alterations in the H3 methylation landscape. Furthermore, the degradation of core histones, including H3.3, by the proteasome activator PA200 is crucial for maintaining the stability of histone marks during transcription and aging, highlighting the importance of H3.3 turnover in preserving chromatin integrity in aging cells.
The specific incorporation of H3.3 into chromatin, which is replication-independent, contrasts with the replication-coupled deposition of canonical H3 variants and is associated with active chromatin states. This unique feature of H3.3 suggests its involvement in regulating gene expression and maintaining chromatin function in slowly replicating or postmitotic cells, which accumulate H3.3 over time, potentially affecting heterochromatin and contributing to aging phenotypes. Moreover, the dynamic changes in H3 proteoforms, including H3.3, throughout the lifespan of mammals, underscore its role in the aging process and suggest that H3.3 variant replacement could influence the chromatin state and function in age-dependent manners.
In the context of neuronal development and aging, H3.3 is crucial for establishing the neuronal transcriptome and identity immediately postmitosis, indicating its role extends beyond merely maintaining histone levels in postmitotic cells to actively shaping the chromatin landscape and gene expression patterns critical for aging. Collectively, these findings underscore the multifaceted role of histone H3.3 in aging, from influencing chromatin dynamics and gene regulation to affecting cellular longevity and organismal aging.
How does the transcriptome of the brain change with age?4 answersThe transcriptome of the brain undergoes changes with age. Overall, decreased synaptic function and increased immune function are prevalent in most regions of the aged brain. In the hippocampus, the expression of phosphoprotein, alternative splicing, and cytoskeleton genes are commonly changed in both aging and Alzheimer's disease (AD), while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Old brains display fewer sex-biased genes, and expression of both male-biased and female-biased genes converges towards a sexually intermediate phenotype with age. There is a weak but reproducible transcriptome-wide shift towards an increase in heterogeneity with age, with more genes significantly increasing their heterogeneity than decreasing it. Chemotherapeutic agents like doxorubicin can induce gene expression changes in the brain similar to those seen in brain aging, potentially leading to impaired cognitive function.
Are there papers in histone 3 is used in fishes?3 answersHistone 3 is indeed used in fishes. Several papers discuss the role of histone 3 in fish development and defense mechanisms. Schuurmans Stekhoven et al. studied extranuclear histones and histone fragments in gill microsomes of teleostean fishes, including tilapia, trout, carp, eel, and elephant fish. Li et al. investigated the change patterns of histone 3 lysine 9 acetylation (H3K9ac) during zebrafish embryo development. Bryant et al. analyzed germline mutations in histone 3 family 3A (H3F3A) or H3F3B in patients with neurologic dysfunction and congenital anomalies. Chaithanya et al. identified a potential antimicrobial peptide sequence of teleostin from histone H2A in marine teleost fishes. Lenin et al. compared histone H2A-derived antimicrobial peptides in commercially important teleost fishes. These papers provide insights into the role of histone 3 in fish biology and highlight its importance in development and defense mechanisms.
How do t cells change in aging?3 answersT cells undergo significant changes during aging. The most notable changes include a reduction in the naive T cell pool and an accumulation of memory-like T cells. These memory-like T cells in older individuals acquire a phenotype of terminally differentiated cells, lose the expression of costimulatory molecules, and exhibit properties of senescent cells. Additionally, aging leads to the development of extremely cytotoxic T cells with natural killer properties, exhausted T cells with altered cytokine production, and regulatory T cells that gain proinflammatory features. Importantly, all of these subsets of age-associated T cells lose their lymph node homing capacity and preferentially migrate to nonlymphoid tissues, contributing to tissue deterioration and inflammaging. Furthermore, age-related changes in T-cell migration are influenced by biophysical parameters, such as nuclear cytoskeleton organization and cell deformability. These changes in T cells play a causal role in mammalian aging, suggesting that targeting naive T cells through apoptosis modulation could offer new therapeutic approaches for aging and age-related diseases. T cell aging is also associated with the breakdown of T cell tolerance and the development of tissue inflammation in autoimmune diseases.
Do epigenetic changes move histones?4 answers
