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.

中文翻译：

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HNRNPL 对整联蛋白和细胞外基质基因的调节是表皮更新所必需的。

分层上皮细胞（例如表皮）需要协调调节干细胞和祖细胞的增殖、存活和分化以维持体内平衡。整合素介导的表皮基底层干细胞通过细胞外基质 (ECM) 蛋白锚定在下面的真皮上对于这一过程至关重要。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，我们展示了 RNA 结合蛋白 (RBP) 异质核核糖核蛋白 L (HNRNPL) 与染色质上的这些基因结合以促进它们的表达。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 转录所必需的。在没有 HNRNPL 的情况下，由于整联蛋白/ECM 表达减少，干细胞所在的表皮基底层过早分化并与下面的真皮分离。我们的结果表明，染色质上的 RBP 通过决定特定类别基因的表达来维持干细胞和祖细胞命运的关键作用。