Chromatin priming elements direct tissue-specific gene activity prior to hematopoietic specification
Chromatin priming elements direct tissue-specific gene activity prior to hematopoietic specification
复制标题
染色质启动元件在造血规范之前指导组织特异性基因活性
DOI：
10.1101/2023.08.30.555485
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Maytum A
中科院分区：
文献类型：
--
作者：
Maytum A
在发育过程中，组织特异性基因调控涉及转录因子和结合增强子和启动子元件的表观遗传调控因子之间的相互作用。活性增强子的模式决定了细胞分化状态。然而，发育性基因激活涉及到一个称为染色质启动的先前步骤，这一步骤尚不完全清楚。我们最近开发了一种全基因组功能测定，使我们能够从功能上识别整合在染色质中的增强子元件，该增强子元件调节了胚胎干细胞向血液的体外分化的五个阶段。我们还测量了整体染色质可及性、组蛋白修饰和转录因子结合。这些数据的整合鉴定和表征了在基因表达开始之前被激活的顺式调控元件，其中一些以信号依赖的方式启动。这种启动元件的缺失导致其相关基因在发育过程中的上调延迟。我们的工作揭示了与早期染色质开放动态相互作用的复杂网络的细节，这是动态组织特异性基因表达控制的核心。
Tissue-specific gene regulation during development involves the interplay between transcription factors and epigenetic regulators binding to enhancer and promoter elements. The pattern of active enhancers defines the cellular differentiation state. However, developmental gene activation involves a previous step called chromatin priming which is not fully understood. We recently developed a genome-wide functional assay that allowed us to functionally identify enhancer elements integrated in chromatin regulating five stages spanning the in vitro differentiation of embryonic stem cells to blood. We also measured global chromatin accessibility, histone modifications, and transcription factor binding. The integration of these data identified and characterised cis-regulatory elements which become activated before the onset of gene expression, some of which are primed in a signalling-dependent fashion. Deletion of such a priming element leads to a delay in the up-regulation of its associated gene in development. Our work uncovers the details of a complex network of regulatory interactions with the dynamics of early chromatin opening being at the heart of dynamic tissue-specific gene expression control.
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影响因子：
30.8
作者：
Luo，Renhe;Yan，Jielin;Beer，Michael A. A.
通讯作者：
Beer，Michael A. A.
影响因子：
30.8
作者：
Huang, Gang;Zhang, Pu;Tenen, Daniel G.
通讯作者：
Tenen, Daniel G.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
20.3
作者：
Lancrin, Christophe;Mazan, Milena;Lacaud, Georges
通讯作者：
Lacaud, Georges