A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification.
A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification.
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DOI：
10.1038/s41467-023-35910-9
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发表时间：
2023-01-17
影响因子：
16.6
通讯作者：
Bonifer, C.
中科院分区：
文献类型：
--
作者：
Edginton-White, B.;Maytum, A.;Kellaway, S. G.;Goode, D. K.;Keane, P.;Pagnuco, I.;Assi, S. A.;Ames, L.;Clarke, M.;Cockerill, P. N.;Gottgens, B.;Cazier, J. B.;Bonifer, C.
基因表达的发育控制关键取决于远端顺式调控元件，包括与启动子相互作用以激活基因表达的增强子。到目前为止，还没有进行全球性的实验，以确定他们的细胞类型和细胞阶段的特定活动在一个发育途径和染色质的情况下。在这里，我们描述了一种高通量的方法，确定了成千上万的差异活性顺式元件能够刺激最小的启动子在造血祖细胞发育的五个阶段，从胚胎干细胞（ES）细胞，它可以适应任何ES细胞衍生的细胞类型。我们表明，血细胞特异性基因表达是由成千上万的分化阶段特异性的顺式元件，响应于细胞因子信号终止于信号响应转录因子的协同作用。我们的工作为造血特化的研究提供了重要的资源，并突出了外部信号如何以及在何处编程细胞类型特异性染色质景观驱动造血分化的机制。定义顺式调控元件是理解基因表达是如何被调控的一个重要目标。在这里，作者表明血细胞特异性基因表达是由数千个分化阶段特异性顺式元件组的作用控制的，这些顺式元件响应于细胞因子信号，终止于信号应答转录因子。
Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. To date no global experiments have been conducted that identify their cell type and cell stage-specific activity within one developmental pathway and in a chromatin context. Here, we describe a high-throughput method that identifies thousands of differentially active cis-elements able to stimulate a minimal promoter at five stages of hematopoietic progenitor development from embryonic stem (ES) cells, which can be adapted to any ES cell derived cell type. We show that blood cell-specific gene expression is controlled by the concerted action of thousands of differentiation stage-specific sets of cis-elements which respond to cytokine signals terminating at signalling responsive transcription factors. Our work provides an important resource for studies of hematopoietic specification and highlights the mechanisms of how and where extrinsic signals program a cell type-specific chromatin landscape driving hematopoietic differentiation. Defining cis-regulatory elements is an important goal in understanding how gene expression is regulated. Here the authors show blood cell-specific gene expression is controlled by the action of thousands of differentiation stage-specific sets of cis-elements that respond to cytokine signals terminating at signaling responsive transcription factors.
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影响因子：
11.8
作者：
Goode DK;Obier N;Vijayabaskar MS;Lie-A-Ling M;Lilly AJ;Hannah R;Lichtinger M;Batta K;Florkowska M;Patel R;Challinor M;Wallace K;Gilmour J;Assi SA;Cauchy P;Hoogenkamp M;Westhead DR;Lacaud G;Kouskoff V;Göttgens B;Bonifer C
通讯作者：
Bonifer C
影响因子：
3.9
作者：
Dogan N;Wu W;Morrissey CS;Chen KB;Stonestrom A;Long M;Keller CA;Cheng Y;Jain D;Visel A;Pennacchio LA;Weiss MJ;Blobel GA;Hardison RC
通讯作者：
Hardison RC
影响因子：
64.5
作者：
Gasperini, Molly;Hill, Andrew J.;Shendure, Jay
通讯作者：
Shendure, Jay
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：
30.8
作者：
Corces, M. Ryan;Buenrostro, Jason D.;Wu, Beijing;Greenside, Peyton G.;Chan, Steven M.;Koenig, Julie L.;Snyder, Michael P.;Pritchard, Jonathan K.;Kundaje, Anshul;Gkeenleaf, William J.;Majeti, Ravindra;Chang, Howard Y.
通讯作者：
Chang, Howard Y.