Construction of an atlas of transcription factor binding during mouse development identifies popular regulatory regions.

IF 3.7 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY
Development Pub Date : 2025-03-15 Epub Date: 2025-03-24 DOI:10.1242/dev.204311
Anna Nordin, Gianluca Zambanini, Mattias Enar Jonasson, Tamina Weiss, Yorick van de Grift, Pierfrancesco Pagella, Claudio Cantù
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引用次数: 0

Abstract

Gene regulators physically associate with the genome, in a combinatorial fashion, to drive tissue-specific gene expression. Uncovering the genome-wide activity of all gene regulators across tissues is therefore needed to understand gene regulation during development. Here, we take a first step towards this goal. Using CUT&RUN, we systematically mapped genome-wide binding profiles of key transcription factors and co-factors that mediate ontogenetically relevant signaling pathways in select mouse tissues at two developmental stages. Computation of the datasets unveiled tissue- and time-specific activity for each gene regulator. We identified 'popular' regulatory regions that are bound by a multitude of regulators, which tend to be more evolutionarily conserved. Consistently, they lie near the transcription start site of genes for which dysregulation results in early embryonic lethality. Moreover, the human homologs of these regions are similarly bound by many gene regulators and are highly conserved, indicating a retained relevance for human development. This work constitutes a decisive step towards understanding how the genome is simultaneously read and used by gene regulators in a holistic fashion to drive embryonic development.

构建小鼠发育过程中转录因子结合的图谱,确定受欢迎的调控区域。
基因调节因子以组合方式与基因组物理关联,以驱动组织特异性基因表达。因此,为了理解发育过程中的基因调控,需要揭示跨组织的所有基因调控的全基因组活性。在这里,我们向这个目标迈出了第一步。使用CUT&RUN,我们系统地绘制了在两个发育阶段的小鼠组织中介导个体遗传相关信号通路的关键转录因子和辅助因子的全基因组结合谱。数据集的计算揭示了每个基因调节因子的组织和时间特异性活性。我们确定了受众多监管机构约束的“流行”监管区域,这些监管机构往往更倾向于进化保守。它们始终位于基因的TSS附近,这些基因的失调会导致早期胚胎死亡。此外,这些区域的人类同源物同样受到许多基因调控因子的约束,并且高度保守,表明它们与人类发育保持着相关性。这项工作是理解基因组如何同时被基因调控因子以整体方式读取和使用以驱动胚胎发育的决定性一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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