Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development
| العنوان: | Dynamic profiling and functional interpretation of histone lysine crotonylation and lactylation during neural development |
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| المؤلفون: | Shang-Kun Dai, Pei-Pei Liu, Xiao Li, Lin-Fei Jiao, Zhao-Qian Teng, Chang-Mei Liu |
| المصدر: | Development. 149 |
| بيانات النشر: | The Company of Biologists, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Histones, Mammals, Lysine, Animals, Acetylation, Protein Processing, Post-Translational, Molecular Biology, Epigenesis, Genetic, Developmental Biology |
| الوصف: | Metabolites such as crotonyl-CoA and lactyl-CoA influence gene expression by covalently modifying histones, known as histone lysine crotonylation (Kcr) and lysine lactylation (Kla). However, the existence patterns, dynamic changes, biological functions and associations of these modifications with histone lysine acetylation and gene expression during mammalian development remain largely unknown. Here, we find that histone Kcr and Kla are widely distributed in the brain and undergo global changes during neural development. By profiling the genome-wide dynamics of H3K9ac, H3K9cr and H3K18la in combination with ATAC and RNA sequencing, we reveal that these marks are tightly correlated with chromatin state and gene expression, and extensively involved in transcriptome remodeling to promote cell-fate transitions in the developing telencephalon. Importantly, we demonstrate that global Kcr and Kla levels are not the consequence of transcription and identify the histone deacetylases (HDACs) 1-3 as novel ‘erasers’ of H3K18la. Using P19 cells as an induced neural differentiation system, we find that HDAC1-3 inhibition by MS-275 pre-activates neuronal transcriptional programs by stimulating multiple histone lysine acylations simultaneously. These findings suggest that histone Kcr and Kla play crucial roles in the epigenetic regulation of neural development. |
| تدمد: | 1477-9129 0950-1991 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3196f6d3d1d1c558ae7802485071f36d https://doi.org/10.1242/dev.200049 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....3196f6d3d1d1c558ae7802485071f36d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779129 09501991 |
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