MyoD induces ARTD1 and nucleoplasmic poly-ADP-ribosylation during fibroblast to myoblast transdifferentiation.

MyoD induces ARTD1 and nucleoplasmic poly-ADP-ribosylation during fibroblast to myoblast transdifferentiation.
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DOI:
10.1016/j.isci.2021.102432
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发表时间:
2021-05-21
期刊:
影响因子:
5.8
通讯作者:
Hottiger MO
Hottiger MO
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Bisceglie L;Hopp AK;Gunasekera K;Wright RH;Le Dily F;Vidal E;Dall'Agnese A;Caputo L;Nicoletti C;Puri PL;Beato M;Hottiger MO

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虽然据报道蛋白质 ADP-核糖基化可调节分化和去分化,但迄今为止尚未在转分化过程中对其进行研究。在这里,我们发现 MyoD 诱导的成纤维细胞向成肌细胞的转分化促进了 ADP-核糖基转移酶 ARTD1 的表达。在转分化过程中通过 Hi-C 和 RNA-seq 分析对基因组结构进行综合分析表明,ARTD1 局部促进 A/B 区室化,并共同调节 MyoD 靶基因的子集,但不足以改变转分化。令人惊讶的是,ARTD1的表达伴随着核ADP核糖基化的持续合成,这种合成既不依赖于细胞周期,也不是由DNA损伤诱导的。与 H2O2 诱导的 ADP 核糖基化相反,MyoD 依赖性 ADP 核糖基化与染色质无关,而是定位于核质。总之,这些数据描述了 MyoD 诱导的核质 ADP-核糖基化,特别是在转分化过程中观察到,因此可能扩展与 ADP-核糖基化相关的大量细胞过程。 IMR90 向成肌细胞的 MyoD 依赖性转分化诱导 ARTD1 表达 转分化在成肌细胞中诱导核 ARTD1 依赖性 ADP 核糖基化 这种 ADP 核糖基化的诱导与细胞周期和 DNA 损伤无关。分子生物学;细胞生物学;发育生物学
While protein ADP-ribosylation was reported to regulate differentiation and dedifferentiation, it has so far not been studied during transdifferentiation. Here, we found that MyoD-induced transdifferentiation of fibroblasts to myoblasts promotes the expression of the ADP-ribosyltransferase ARTD1. Comprehensive analysis of the genome architecture by Hi-C and RNA-seq analysis during transdifferentiation indicated that ARTD1 locally contributed to A/B compartmentalization and coregulated a subset of MyoD target genes that were however not sufficient to alter transdifferentiation. Surprisingly, the expression of ARTD1 was accompanied by the continuous synthesis of nuclear ADP ribosylation that was neither dependent on the cell cycle nor induced by DNA damage. Conversely to the H2O2-induced ADP-ribosylation, the MyoD-dependent ADP-ribosylation was not associated to chromatin but rather localized to the nucleoplasm. Together, these data describe a MyoD-induced nucleoplasmic ADP-ribosylation that is observed particularly during transdifferentiation and thus potentially expands the plethora of cellular processes associated with ADP-ribosylation. MyoD-dependent transdifferentiation of IMR90 to myoblasts induces ARTD1 expression Transdifferentiation induces nuclear ARTD1-dependent ADP-ribosylation in myoblasts This ADP-ribosylation is induced independent of cell cycle and of DNA damage ARTD1-mediated poly-ADP-ribosylation localizes to the nucleoplasm in myoblasts Biological Sciences; Molecular Biology; Cell Biology; Developmental Biology
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