Recognition of H2AK119ub plays an important role in RSF1-regulated early Xenopus development.
Recognition of H2AK119ub plays an important role in RSF1-regulated early Xenopus development.
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DOI：
10.3389/fcell.2023.1168643
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
多梳族蛋白（Polycomb group，PcG）是通过共价修饰组蛋白来调控基因表达和发育的关键蛋白，但对组蛋白修饰标志物调控胚胎发生的机制研究较少。我们先前鉴定了重构和间隔因子1（RSF 1）作为组蛋白H2 A赖氨酸119泛素化（H2 AK 119 ub）的阅读器，H2 AK 119 ub是由Polycomb抑制复合物1（PRC 1）沉积的组蛋白标记。在目前的研究中，我们使用非洲爪蟾作为模型来研究RSF 1如何影响早期胚胎发育，以及H2 AK 119 ub的识别是否对RSF 1的功能很重要。我们发现，敲除非洲爪蟾RSF 1，rsf 1，不仅诱导原肠胚形成缺陷，如前所述，但特定的有针对性的敲除在前瞻性的神经前体诱导神经和神经嵴缺陷，减少标记基因。此外，与非洲爪蟾PRC 1基因敲除相似，rsf 1基因敲除胚胎的前后神经模式也受到影响。H2 AK 119 ub的结合似乎是rsf 1功能的关键，作为一个构建体与UAB结构域，这是RSF 1识别H2 AK 119 ub核小体所需的缺失，未能拯救rsf 1变形胚胎，并在干扰早期非洲爪蟾发育异位表达时效果较差。此外，使用ring 1a-smad 2融合蛋白将H2 AK 119 ub异位沉积在Smad 2靶基因gsc上导致RSF 1的异位募集。该融合蛋白在诱导动物区域中的中胚层标记物或在腹侧组织中表达时的次级轴中是低效的。两者合计，我们的研究结果表明，RSF 1调制类似的早期非洲爪蟾胚胎的发育过程中的PRC 1的组件，RSF 1的行为至少部分通过结合H2 AK 119 ub标记通过UAB域在发展过程中。
Polycomb group (PcG) proteins are key regulators of gene expression and developmental programs via covalent modification of histones, but the factors that interpret histone modification marks to regulate embryogenesis are less studied. We previously identified Remodeling and Spacing Factor 1 (RSF1) as a reader of histone H2A lysine 119 ubiquitination (H2AK119ub), the histone mark deposited by Polycomb Repressive Complex 1 (PRC1). In the current study, we used Xenopus laevis as a model to investigate how RSF1 affects early embryonic development and whether recognition of H2AK119ub is important for the function of RSF1. We showed that knockdown of Xenopus RSF1, rsf1, not only induced gastrulation defects as reported previously, but specific targeted knockdown in prospective neural precursors induced neural and neural crest defects, with reductions of marker genes. In addition, similar to knockdown of PRC1 components in Xenopus, the anterior-posterior neural patterning was affected in rsf1 knockdown embryos. Binding of H2AK119ub appeared to be crucial for rsf1 function, as a construct with deletion of the UAB domain, which is required for RSF1 to recognize the H2AK119ub nucleosomes, failed to rescue rsf1 morphant embryos and was less effective in interfering with early Xenopus development when ectopically expressed. Furthermore, ectopic deposition of H2AK119ub on the Smad2 target gene gsc using a ring1a-smad2 fusion protein led to ectopic recruitment of RSF1. The fusion protein was inefficient in inducing mesodermal markers in the animal region or a secondary axis when expressed in the ventral tissues. Taken together, our results reveal that rsf1 modulates similar developmental processes in early Xenopus embryos as components of PRC1 do, and that RSF1 acts at least partially through binding to the H2AK119ub mark via the UAB domain during development.
Polycomb Repressive Complex 2 在胚胎干细胞分化过程中调节谱系保真度。
影响因子：
3.7
作者：
Thornton SR;Butty VL;Levine SS;Boyer LA
通讯作者：
Boyer LA
影响因子：
4.5
作者：
Hanai K;Furuhashi H;Yamamoto T;Akasaka K;Hirose S
通讯作者：
Hirose S
DOI：
10.1002/dvdy.319
发表时间：
2021-08
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
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作者：
Tien CL;Mohammadparast S;Chang C
通讯作者：
Chang C