論文 - 詳細
| RRC ID | 69992 |
|---|---|
| 著者 | Lowden C, Boulet A, Boehler NA, Seecharran S, Rios Garcia J, Lowe NJ, Liu J, Ong JLK, Wang W, Ma L, Cheng AH, Senatore A, Monks DA, Liu BH, Leary SC, Cheng HM. |
| タイトル | Homeostatic control of nuclear-encoded mitochondrial gene expression by the histone variant H2A.Z is essential for neuronal survival. |
| ジャーナル | Cell Rep |
| Abstract |
Histone variants are crucial regulators of chromatin structure and gene transcription, yet their functions within the brain remain largely unexplored. Here, we show that the H2A histone variant H2A.Z is essential for neuronal survival. Mice lacking H2A.Z in GABAergic neurons or Purkinje cells (PCs) present with a progressive cerebellar ataxia accompanied by widespread degeneration of PCs. Ablation of H2A.Z in other neuronal subtypes also triggers cell death. H2A.Z binds to the promoters of key nuclear-encoded mitochondrial genes to regulate their expression and promote organelle function. Bolstering mitochondrial activity genetically or by organelle transplant enhances the survival of H2A.Z-ablated neurons. Changes in bioenergetic status alter H2A.Z occupancy at the promoters of nuclear-encoded mitochondrial genes, an adaptive response essential for cell survival. Our results highlight that H2A.Z fulfills a key, conserved role in neuronal survival by acting as a transcriptional rheostat to regulate the expression of genes critical to mitochondrial function. |
| 巻・号 | 36(11) |
| ページ | 109704 |
| 公開日 | 2021-9-14 |
| DOI | 10.1016/j.celrep.2021.109704 |
| PII | S2211-1247(21)01151-7 |
| PMID | 34525369 |
| MeSH | Animals Cell Nucleus / metabolism* Cell Survival / drug effects Cells, Cultured Down-Regulation Fibroblasts / cytology Fibroblasts / metabolism GABAergic Neurons / cytology GABAergic Neurons / metabolism Histones / deficiency Histones / genetics* Histones / metabolism Metformin / pharmacology Mice Mice, Inbred C57BL Mice, Knockout Mitochondria / genetics Mitochondria / metabolism* Mitochondrial Proteins / metabolism NF-E2-Related Factor 2 / genetics NF-E2-Related Factor 2 / metabolism Oxidative Phosphorylation Purkinje Cells / cytology Purkinje Cells / metabolism Transcriptome* / drug effects Up-Regulation |
| IF | 8.109 |
| リソース情報 | |
| 実験動物マウス | RBRC05765 |