Conserved paradoxical relationships among the evolutionary, structural and expressional features of KRAB zinc-finger proteins reveal their special functional characteristics.
Conserved paradoxical relationships among the evolutionary, structural and expressional features of KRAB zinc-finger proteins reveal their special functional characteristics.
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KRAB锌指蛋白的进化、结构和表达特征之间保守的矛盾关系揭示了其特殊的功能特征
DOI：
10.1186/s12860-021-00346-w
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发表时间：
2021-01-22
影响因子：
2.8
通讯作者：
Yang D
中科院分区：
文献类型：
--
作者：
Shen P;Xu A;Hou Y;Wang H;Gao C;He F;Yang D
背景含KRAB结构域的大锌指蛋白（KZFP）家族的一个显着特征是其快速进化，导致在某个哺乳动物基因组中产生数百个具有不同起源时间的成员基因。然而，缺乏对不同起源时间的 KZFP 的结构和表达特征进行全面的全基因组和跨分类群分析。这种类型的分析将为了解这个特殊家族的功能特征提供有价值的线索。结果在这项研究中，我们发现了关于这个问题的几个保守的矛盾现象。 1）普通的年轻结构域/蛋白质往往是无序的，但大多数KRAB结构域在肉翅目超纲的64个代表性物种中是完全结构化的，并且大多数KZFP也是高度结构化的，表明其刚性和独特的结构和功能特征；作为例外，旧的含锌指 KZFP 具有相对无序的 KRAB 结构域和连接区，有助于形成多样化的相互作用伙伴和功能。 2）一般来说，年轻或高度结构化的蛋白质往往具有时空特异性并且丰度较低。然而，通过对29个RNA-seq数据集（包括7种哺乳动物的早期胚胎发育、胚胎干细胞分化、胚胎和成体器官、组织的725个样本）的综合分析，我们发现无论进化年龄和结构紊乱程度如何，KZFPs都倾向于以中等丰度普遍表达，这表明KZFPs在不同状态下具有广泛的功能需求。 3）聚类和相关分析表明，不同时空状态之间存在差异表达模式，表明特异性高表达的KZFPs可能在相应状态中发挥重要作用。特别是，部分含有年轻锌指的KZFP在早期胚胎发育和ESC分化为内胚层或中胚层时高表达。共表达分析表明，含有年轻锌指的 KZFP 在五个共表达模块中显着富集。其中，包括13个年轻锌指的KZFP在内的一个模块表现出“早期高、晚期低”的表达模式。进一步的功能分析表明，它们可能通过参与细胞周期相关过程，在早期胚胎发育和ESC分化中发挥作用。结论本研究展示了KZFPs保守且特殊的结构、表达特征，为了解其功能特征及其快速进化的潜在原因提供了新的线索。
BackgroundOne striking feature of the large KRAB domain-containing zinc finger protein (KZFP) family is its rapid evolution, leading to hundreds of member genes with various origination time in a certain mammalian genome. However, a comprehensive genome-wide and across-taxa analysis of the structural and expressional features of KZFPs with different origination time is lacking. This type of analysis will provide valuable clues about the functional characteristics of this special family.ResultsIn this study, we found several conserved paradoxical phenomena about this issue. 1) Ordinary young domains/proteins tend to be disordered, but most of KRAB domains are completely structured in 64 representative species across the superclass of Sarcopterygii and most of KZFPs are also highly structured, indicating their rigid and unique structural and functional characteristics; as exceptions, old-zinc-finger-containing KZFPs have relatively disordered KRAB domains and linker regions, contributing to diverse interacting partners and functions. 2) In general, young or highly structured proteins tend to be spatiotemporal specific and have low abundance. However, by integrated analysis of 29 RNA-seq datasets, including 725 samples across early embryonic development, embryonic stem cell differentiation, embryonic and adult organs, tissues in 7 mammals, we found that KZFPs tend to express ubiquitously with medium abundance regardless of evolutionary age and structural disorder degree, indicating the wide functional requirements of KZFPs in various states. 3) Clustering and correlation analysis reveal that there are differential expression patterns across different spatiotemporal states, suggesting the specific-high-expression KZFPs may play important roles in the corresponding states. In particular, part of young-zinc-finger-containing KZFPs are highly expressed in early embryonic development and ESCs differentiation into endoderm or mesoderm. Co-expression analysis revealed that young-zinc-finger-containing KZFPs are significantly enriched in five co-expression modules. Among them, one module, including 13 young-zinc-finger-containing KZFPs, showed an ‘early-high and late-low’ expression pattern. Further functional analysis revealed that they may function in early embryonic development and ESC differentiation via participating in cell cycle related processes.ConclusionsThis study shows the conserved and special structural, expressional features of KZFPs, providing new clues about their functional characteristics and potential causes of their rapid evolution.
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影响因子：
64.8
作者：
Jacobs, Frank M. J.;Greenberg, David;Ngan Nguyen;Haeussler, Maximilian;Ewing, Adam D.;Katzman, Sol;Paten, Benedict;Salama, Sofie R.;Haussler, David
通讯作者：
Haussler, David
适应性免疫系统中的克鲁佩尔相关盒 (KRAB) 蛋白。
DOI：
10.4161/nucl.28738
发表时间：
2014-03
期刊：
Nucleus (Austin, Tex.)
影响因子：
--
作者：
Santoni de Sio FR
通讯作者：
Santoni de Sio FR
跨物种蛋白质丰度的蛋白质组范围分布的规律模式
影响因子：
3.7
作者：
Zhong F;Yang D;Hao Y;Lin C;Jiang Y;Ying W;Wu S;Zhu Y;Liu S;Yang P;Qian X;He F
通讯作者：
He F
影响因子：
11.8
作者：
Imbeault M;Trono D
通讯作者：
Trono D
影响因子：
16.6
作者：
Chen, Wanze;Schwalie, Petra C.;Deplancke, Bart
通讯作者：
Deplancke, Bart