Regulation of integrin and extracellular matrix genes by HNRNPL is necessary for epidermal renewal.
Regulation of integrin and extracellular matrix genes by HNRNPL is necessary for epidermal renewal.
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HNRNPL对整合素和细胞外基质基因的调节是表皮更新所必需的。
DOI：
10.1371/journal.pbio.3001378
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发表时间：
2021-09
期刊：
影响因子：
9.8
通讯作者：
Sen GL
中科院分区：
文献类型：
--
作者：
Li J;Chen Y;Tiwari M;Bansal V;Sen GL
分层上皮细胞如表皮需要协调调节干细胞和祖细胞增殖、存活和分化以维持稳态。整合素介导的表皮基底层干细胞通过细胞外基质（ECM）蛋白锚定到下面的真皮是这个过程的关键。目前尚不清楚这些整合素和ECM基因的表达是如何调节的。在这里，我们表明，RNA结合蛋白（RBP）异质核核糖核蛋白L（HNRNPL）结合到这些基因的染色质，以促进其表达。HNRNPL将RNA聚合酶II（Pol II）募集到整合素/ECM基因，并且是通过这些基因稳定Pol II转录所需的。在不存在HNRNPL的情况下，由于整合素/ECM表达减少，干细胞所在的表皮基底层过早分化并与下层真皮分离。我们的研究结果表明，染色质上的RBPs通过决定特定类型基因的表达来维持干细胞和祖细胞的命运。表皮的维持需要表皮的基底层干细胞通过细胞外基质（ECM）蛋白质与下层真皮的整合素介导的锚定。这项研究表明，RNA结合蛋白HNRNPL结合到编码整合素和ECM蛋白的基因的染色质上，通过稳定RNA聚合酶II介导的转录来促进其表达。在没有HNRNPL的情况下，表皮的基底层过早分化和分离。
Stratified epithelia such as the epidermis require coordinated regulation of stem and progenitor cell proliferation, survival, and differentiation to maintain homeostasis. Integrin-mediated anchorage of the basal layer stem cells of the epidermis to the underlying dermis through extracellular matrix (ECM) proteins is crucial for this process. It is currently unknown how the expression of these integrins and ECM genes are regulated. Here, we show that the RNA-binding protein (RBP) heterogeneous nuclear ribonucleoprotein L (HNRNPL) binds to these genes on chromatin to promote their expression. HNRNPL recruits RNA polymerase II (Pol II) to integrin/ECM genes and is required for stabilizing Pol II transcription through those genes. In the absence of HNRNPL, the basal layer of the epidermis where the stem cells reside prematurely differentiates and detaches from the underlying dermis due to diminished integrin/ECM expression. Our results demonstrate a critical role for RBPs on chromatin to maintain stem and progenitor cell fate by dictating the expression of specific classes of genes. Maintenance of the epidermis requires integrin-mediated anchorage of basal layer stem cells of the epidermis to the underlying dermis via extracellular matrix (ECM) proteins. This study shows that the RNA binding protein HNRNPL binds to the chromatin of genes encoding integrin and ECM proteins to promote their expression by stabilizing RNA polymerase II-mediated transcription. In the absence of HNRNPL, the basal layer of the epidermis prematurely differentiates and detaches.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
DOI：
10.1083/jcb.200209016
发表时间：
2003-02-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Evans RD;Perkins VC;Henry A;Stephens PE;Robinson MK;Watt FM
通讯作者：
Watt FM
影响因子：
64.5
作者：
Ji X;Zhou Y;Pandit S;Huang J;Li H;Lin CY;Xiao R;Burge CB;Fu XD
通讯作者：
Fu XD
影响因子：
3.7
作者：
Banno, Tomohiro;Blumenberg, Miroslav
通讯作者：
Blumenberg, Miroslav
影响因子：
6.5
作者：
Brown, TA;Gil, SG;Carter, WG
通讯作者：
Carter, WG