Chromatin remodeling enzyme Snf2h regulates embryonic lens differentiation and denucleation
Autor: | Qing Xie, Wei Liu, Lisa A. Brennan, Jiri Zavadil, Tomas Stopka, Marc Kantorow, Juraj Kokavec, Winfried Edelmann, Harry Hou, Arthur I. Skoultchi, Romit Majumdar, Shuying He, Saima Limi, Ales Cvekl, Ruth Ashery-Padan, Rebecca McGreal, Wanda Lee Kantorow |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
PAX6 Transcription Factor Chromosomal Proteins Non-Histone Cellular differentiation Biology Models Biological Chromatin remodeling 03 medical and health sciences Heat Shock Transcription Factors Lens Crystalline medicine Transcriptional regulation Autophagy Animals Molecular Biology Adenosine Triphosphatases Cell Nucleus Mice Knockout Cell Cycle DNA Helicases Mitophagy Gene Expression Regulation Developmental Nuclear Proteins Cell Differentiation Epithelial Cells Chromatin Assembly and Disassembly Embryo Mammalian Lens Fiber Chromatin Cell biology Cell Compartmentation DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Fiber cell Lens (anatomy) Mutation Female Lens fiber cell differentiation Transcriptome Developmental Biology Transcription Factors Research Article |
Zdroj: | Development (Cambridge, England). 143(11) |
ISSN: | 1477-9129 |
Popis: | Ocular lens morphogenesis is a model for investigating mechanisms of cellular differentiation, spatial and temporal gene expression control, and chromatin regulation. Brg1 (Smarca4) and Snf2h (Smarca5) are catalytic subunits of distinct ATP-dependent chromatin remodeling complexes implicated in transcriptional regulation. Previous studies have shown that Brg1 regulates both lens fiber cell differentiation and organized degradation of their nuclei (denucleation). Here, we employed a conditional Snf2hflox mouse model to probe the cellular and molecular mechanisms of lens formation. Depletion of Snf2h induces premature and expanded differentiation of lens precursor cells forming the lens vesicle, implicating Snf2h as a key regulator of lens vesicle polarity through spatial control of Prox1, Jag1, p27Kip1 (Cdkn1b) and p57Kip2 (Cdkn1c) gene expression. The abnormal Snf2h−/− fiber cells also retain their nuclei. RNA profiling of Snf2h−/− and Brg1−/− eyes revealed differences in multiple transcripts, including prominent downregulation of those encoding Hsf4 and DNase IIβ, which are implicated in the denucleation process. In summary, our data suggest that Snf2h is essential for the establishment of lens vesicle polarity, partitioning of prospective lens epithelial and fiber cell compartments, lens fiber cell differentiation, and lens fiber cell nuclear degradation. |
Databáze: | OpenAIRE |
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