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
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
Externí odkaz: