Acoel genome reveals the regulatory landscape of whole-body regeneration
Acoel genome reveals the regulatory landscape of whole-body regeneration
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DOI：
10.1126/science.aau6173
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发表时间：
2019-03-15
期刊：
影响因子：
56.9
通讯作者：
Srivastava, Mansi
中科院分区：
文献类型：
--
作者：
Gehrke, Andrew R.;Neverett, Emily;Srivastava, Mansi
全身再生伴随着复杂的转录组学变化，但介导这种动态反应的染色质调控景观仍然未被探索。为了破译协调再生的调控逻辑，我们对体腔蠕虫Hofstenia miamia的基因组进行了测序，Hofstenia miamia是其他两侧对称的姐妹谱系的高度再生成员。表观基因组分析揭示了数千个再生响应染色质区域，并确定了动态结合的转录因子基序，早期生长反应（EGR）结合位点是霍夫斯台尼亚再生过程中最容易接近的。将Egr抑制与染色质分析相结合表明，Egr作为先锋因子直接调节早期创伤诱导基因。通过这种方法推断出的遗传联系允许构建用于全身再生的基因调控网络，从而能够基于基因组学对不同物种的再生进行比较。
Whole-body regeneration is accompanied by complex transcriptomic changes, yet the chromatin regulatory landscapes that mediate this dynamic response remain unexplored. To decipher the regulatory logic that orchestrates regeneration, we sequenced the genome of the acoel worm Hofstenia miamia, a highly regenerative member of the sister lineage of other bilaterians. Epigenomic profiling revealed thousands of regeneration-responsive chromatin regions and identified dynamically bound transcription factor motifs, with the early growth response (EGR) binding site as the most variably accessible during Hofstenia regeneration. Combining egr inhibition with chromatin profiling suggests that Egr functions as a pioneer factor to directly regulate early wound-induced genes. The genetic connections inferred by this approach allowed the construction of a gene regulatory network for whole-body regeneration, enabling genomics-based comparisons of regeneration across species.