Characterising open chromatin in chick embryos identifies cis-regulatory elements important for paraxial mesoderm formation and axis extension.
Characterising open chromatin in chick embryos identifies cis-regulatory elements important for paraxial mesoderm formation and axis extension.
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DOI：
10.1038/s41467-021-21426-7
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发表时间：
2021-02-19
影响因子：
16.6
通讯作者：
Münsterberg AE
中科院分区：
文献类型：
--
作者：
Mok GF;Folkes L;Weldon SA;Maniou E;Martinez-Heredia V;Godden AM;Williams RM;Sauka-Spengler T;Wheeler GN;Moxon S;Münsterberg AE
由近轴中胚层产生的体节是节段性脊椎动物身体计划的标志。它们在轴伸展过程中按顺序形成，并产生肌肉骨骼细胞谱系。轴旁中胚层如何沿轴向区域化，以及这与染色质可及性和转录组的动态变化之间的关系尚不清楚。在这里，我们报告了沿鸡胚轴的ATAC-seq和RNA-seq的时空序列。足迹分析表明，几个关键转录因子的结合位点的覆盖范围不同，包括CDX2、LEF1和HOX簇的成员。将可获得的染色质与附近表达的基因相关联，可识别Tcf15和MEOX1的顺式调节元件(Cre)。我们确定了它们在非洲爪哇和人类中的时空活性和进化保守性。内源性Cres的表观基因组沉默破坏了Tcf15和MEOX1基因的表达，并概括了前后轴伸展的表型异常。我们的集成方法允许在体内解剖旁轴中胚层调控电路，并对研究基因调控网络具有重要意义。轴旁中胚层的形成和分化是如何调节的，目前尚不清楚。在这里，作者确定了可获得的染色质和基因表达特征，这些特征定义了鸡近轴中胚层发育的不同阶段，并确定了对脊椎动物前后轴形成重要的Cres。
Somites arising from paraxial mesoderm are a hallmark of the segmented vertebrate body plan. They form sequentially during axis extension and generate musculoskeletal cell lineages. How paraxial mesoderm becomes regionalised along the axis and how this correlates with dynamic changes of chromatin accessibility and the transcriptome remains unknown. Here, we report a spatiotemporal series of ATAC-seq and RNA-seq along the chick embryonic axis. Footprint analysis shows differential coverage of binding sites for several key transcription factors, including CDX2, LEF1 and members of HOX clusters. Associating accessible chromatin with nearby expressed genes identifies cis-regulatory elements (CRE) for TCF15 and MEOX1. We determine their spatiotemporal activity and evolutionary conservation in Xenopus and human. Epigenome silencing of endogenous CREs disrupts TCF15 and MEOX1 gene expression and recapitulates phenotypic abnormalities of anterior–posterior axis extension. Our integrated approach allows dissection of paraxial mesoderm regulatory circuits in vivo and has implications for investigating gene regulatory networks. How paraxial mesoderm formation and differentiation is regulated is unclear. Here, the authors identify accessible chromatin and gene expression signatures that define different stages of paraxial mesoderm development in the chick and identify CREs important for vertebrate anterior–posterior axis formation.
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影响因子：
2.4
作者：
Berti F;Nogueira JM;Wöhrle S;Sobreira DR;Hawrot K;Dietrich S
通讯作者：
Dietrich S
影响因子：
30.8
作者：
Fulco, Charles P.;Nasser, Joseph;Engreitz, Jesse M.
通讯作者：
Engreitz, Jesse M.
影响因子：
64.8
作者：
Dubrulle, J;Pourquié, O
通讯作者：
Pourquié, O
DOI：
10.1073/pnas.0401654101
发表时间：
2004-05-18
影响因子：
11.1
作者：
Chawengsaksophak, K;de Graaff, W;Beck, F
通讯作者：
Beck, F
影响因子：
2.5
作者：
Bothe, Ingo;Dietrich, Susanne
通讯作者：
Dietrich, Susanne