NuRD-independent Mi-2 activity represses ectopic gene expression during neuronal maturation.
NuRD-independent Mi-2 activity represses ectopic gene expression during neuronal maturation.
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DOI：
10.15252/embr.202255362
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发表时间：
2023-04-05
期刊：
影响因子：
7.7
通讯作者：
中科院分区：
文献类型：
--
作者：
在神经元发育过程中，染色质状态发生广泛的变化，以调节谱系特异性基因的表达。分化神经元中抑制非神经元基因的分子因素尚未明确。Mi2/NuRD复合物是一种多蛋白复合物，具有核小体重塑和组蛋白去乙酰化酶活性。虽然NuRD先前被认为与神经系统组织的发育有关，但它协调的基因表达程序的确切性质尚不明确。此外，来自几个物种的证据表明，Mi - 2可能被纳入多种复合物中，而这些复合物可能不具有组蛋白去乙酰化酶活性。我们发现，Mi‐2活性是抑制神经元中独立于HDAC1/NuRD的种系基因异位表达所必需的，而NuRD的成分，包括Mi‐2，调节神经基因表达，以确保幼虫神经系统的正常发育。我们发现基因组中的Mi - 2结合在神经元成熟过程中是动态的，并且Mi - 2介导的异位基因表达抑制仅限于神经元发育的早期阶段，这表明在神经元分化的早期阶段，Mi - 2/NuRD是建立稳定的神经元转录组所必需的。本研究确定了保守的染色质重塑剂Mi - 2在抑制神经元发育中谱系不合适基因的表达中的组蛋白去乙酰化酶独立作用。这种功能仅限于神经元谱系的早期发育阶段。
During neuronal development, extensive changes to chromatin states occur to regulate lineage‐specific gene expression. The molecular factors underlying the repression of non‐neuronal genes in differentiated neurons are poorly characterised. The Mi2/NuRD complex is a multiprotein complex with nucleosome remodelling and histone deacetylase activity. Whilst NuRD has previously been implicated in the development of nervous system tissues, the precise nature of the gene expression programmes that it coordinates is ill‐defined. Furthermore, evidence from several species suggests that Mi‐2 may be incorporated into multiple complexes that may not possess histone deacetylase activity. We show that Mi‐2 activity is required for suppressing ectopic expression of germline genes in neurons independently of HDAC1/NuRD, whilst components of NuRD, including Mi‐2, regulate neural gene expression to ensure proper development of the larval nervous system. We find that Mi‐2 binding in the genome is dynamic during neuronal maturation, and Mi‐2‐mediated repression of ectopic gene expression is restricted to the early stages of neuronal development, indicating that Mi‐2/NuRD is required for establishing stable neuronal transcriptomes during the early stages of neuronal differentiation. This study identifies a histone deacetylase‐independent role for the conserved chromatin remodeler Mi‐2 in repressing the expression of lineage inappropriate genes in neuronal development. This function is restricted to early developmental stages of the neuronal lineage.
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DOI：
10.1093/g3journal/jkaa005
发表时间：
2021-01-18
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Aughey GN;Delandre C;McMullen JPD;Southall TD;Marshall OJ
通讯作者：
Marshall OJ
影响因子：
64.5
作者：
Huang, Z;Kunes, S
通讯作者：
Kunes, S
影响因子：
4.5
作者：
Schneiderman JI;Goldstein S;Ahmad K
通讯作者：
Ahmad K
影响因子：
2.4
作者：
Estacio-Gomez, Alicia;Hassan, Amira;Southall, Tony D.
通讯作者：
Southall, Tony D.
影响因子：
64.8
作者：
Ho, Joshua W. K.;June, Youngsook L.;Liu, Tao;Alver, Burak H.;Lee, Soohyun;Ikegami, Kohta;Sohn, Kyung-Ah;Minoda, Aki;Tolstorukov, Michael Y.;Appert, Alex;Parker, Stephen C. J.;Gu, Tingting;Kundaje, Anshul;Riddle, Nicole C.;Bishop, Eric;Egelhofer, Thea A.;Hu, Sheng'en Shawn;Alekseyenko, Artyom A.;Rechtsteiner, Andreas;Asker, Dalal;Belsky, Jason A.;Bowmanm, Sarah K.;Chens, Q. Brent;Chen, Ron A. -J.;Day, Daniel S.;Dong, Yan;Dose, Andrea C.;Duan, Xikun;Epstein, Charles B.;Ercan, Sevinc;Feingold, Elise A.;Ferrari, Francesco;Garrigues, Jacob M.;Gehlenborg, Nils;Good, Peter J.;Haseley, Psalm;He, Daniel;Herrmann, Moritz;Hoffman, Michael M.;Jeffers, Tess E.;Kharchenko, Peter V.;Kolasinska-Zwierz, Paulina;Kotwaliwale, Chitra V.;Kumar, Nischay;Langley, Sasha A.;Larschan, Erica N.;Latorre, Isabel;Libbrecht, Maxwell W.;Lin, Xueqiu;Park, Richard;Pazin, Michael J.;Pham, Hoang N.;Plachetka, Annette;Qin, Bo;Schwartz, Yuri B.;Shoresh, Noam;Stempor, Przemyslaw;Vielle, Anne;Wang, Chengyang;Whittle, Christina M.;Xue, Huiling;Kingstonm, Robert E.;Kim, Ju Han;Bernstein, Bradley E.;Dernburg, Abby F.;Pirrotta, Vincenzo;Kuroda, Mitzi I.;Noble, William S.;Tullius, Thomas D.;Kellis, Manolis;MacAlpine, David M.;Strome, Susan;Elgin, Sarah C. R.;Liu, Xiaole Shirley;Lieb, Jason D.;Ahringer, Julie;Karpen, Gary H.;Park, Peter J.
通讯作者：
Park, Peter J.