Regulation of integrin and extracellular matrix genes by HNRNPL is necessary for epidermal renewal

• Published in: PLoS biology Vol. 19; no. 9; p. e3001378
• Main Authors: Li, Jingting, Chen, Yifang, Tiwari, Manisha, Bansal, Varun, Sen, George L.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.09.2021; Public Library of Science (PLoS)
• Subjects: Apoptosis; Biology and Life Sciences; Cell Differentiation; Cell fate; Cell proliferation; Cell survival; Cells, Cultured; Chromatin; Dermis; DNA-directed RNA polymerase; Epidermal Cells - metabolism; Epidermis; Epidermis - growth & development; Extracellular matrix; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Gene expression; Genes; Heterogeneous-Nuclear Ribonucleoprotein L - metabolism; Homeostasis; Humans; Integrins; Integrins - genetics; Integrins - metabolism; Medicine and Health Sciences; Mutation; Physiological aspects; Progenitor cells; Proteins; Ribonucleic acid; RNA; RNA polymerase; RNA polymerase II; RNA-binding protein; Short Reports; Signal transduction; Skin; Stem Cells; Transcription; United States
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3001378

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.