Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer

Reconstruction of Hypopharyngeal and Esophageal Defects Using a Gastric Tube after Total Esophagectomy and Pharyngolaryngectomy

Retinoblastoma-Binding Protein 4 (RBBP4) is a chromatin adaptor protein that associates with numerous activating and repressive chromatin regulatory complexes. RBBP4 is overexpressed in human gliomas, and has been shown to promote survival of GBM cells and p300-dependent expression of DNA repair genes (Kitange et al., 2016). We previously established a zebrafish RB-defective neural progenitor-like brain tumor model (Solin et al., 2015) and recently found Rbbp4 is highly upregulated in the RBbrain tumors. Here we demonstrate Rbbp4 is essential for zebrafish brain development and show it has distinct requirements in neural stem and progenitor cells. CRISPR/Cas9 targeting was used to isolate a 4 base-pair frameshift mutation in the zebrafish homolog rbbp4. Homozygous mutant rbbp4Δ4/Δ4 are lethal at approximately 5-7 days post fertilization and show a dramatic reduction in the size of the brain and retina. Overexpression of rbbp4 cDNA in a Tg(Tol2) transgenic line rescues the rbbp4 mutant phenotype, demonstrating disruption of neurogenesis in rbbp4Δ4/Δ4 homozygotes is due to lack of functional Rbbp4. Beginning at 2 days post fertilization, γH2AX and activated caspase labeling was detected in post-mitotic regions in the larval midbrain and retina, suggesting RBBP4 is required to prevent DNA-damage and apoptosis in neural progenitors or newborn neurons. γ-H2AX and caspase were not detected in the stem cell niches at the brain ventricle or retinal ciliary marginal zone, however, stem cell morphology was abnormally large. Pulse chase BrdU labeling experiments confirmed a delay in stem cell proliferation and a lack of survival of postmitotic neural progenitors. TP53 morpholino knockdown in rbbp4Δ4/Δ4 homozygotes transiently suppressed neural progenitor apoptosis, indicating the absence of Rbbp4

https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=7465&context=etd

Using zebrafish to elucidate the epigenetic mechanisms controlling neurogenesis and brain tumorigenesis

Human immunodeficiency virus (HIV) transcription is closely associated with chromatin remodeling. Retinoblastoma binding protein 4 (RBBP4) is a histone chaperone implicated in chromatin remodeling. However, the role of RBBP4 in HIV-1 infection and the underlying mechanism remain elusive. In the present study, we showed that RBBP4 plays a negative regulatory role during HIV-1 infection. RBBP4 expression was significantly increased in HIV-1-infected T cells. RBBP4 binds to the HIV-1 long terminal repeat (LTR)， represses HIV-1 LTR-mediated transcription through recruiting nuclear receptor subfamily 2 group F member 1(NR2F1) and histone deacetylase 1 and 2 (HDAC1/2) to HIV-1 LTR, and further controls local histone 3 (H3) deacetylation and chromatin compaction. Furthermore, the occupancy of RBBP4, HDAC1/2, and NR2F1 on LTR in HIV-latent J-lat cells was significantly higher than that in HIV-1-activated cells. In conclusion, our results establish RBBP4 as a new potent antiretroviral factor, which may provide theoretical basis for the treatment of HIV in the future.

Retinoblastoma binding protein 4 represses HIV-1 long terminal repeat-mediated transcription by recruiting NR2F1 and histone deacetylase

Histone chaperones serve a pivotal role in maintaining human physiological processes. They interact with histones in a stable manner, ensuring the accurate and efficient execution of DNA replication, repair and transcription. Retinoblastoma binding protein (RBBP)4 and RBBP7 represent a crucial pair of histone chaperones, which not only govern the molecular behavior of histones H3 and H4, but also participate in the functions of several protein complexes, such as polycomb repressive complex 2 and nucleosome remodeling and deacetylase, thereby regulating the cell cycle, histone modifications, DNA damage and cell fate. A strong association has been indicated between RBBP4/7 and some major human diseases, such as cancer, age-related memory loss and infectious diseases. The present review assesses the molecular mechanisms of RBBP4/7 in regulating cellular biological processes, and focuses on the variations in RBBP4/7 expression and their potential mechanisms in various human diseases, thus providing new insights for their diagnosis and treatment.

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review)

RbAp48 Is Critical for the Proliferation of Hypopharyngeal Carcinoma

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RbAp48 Is Critical for the Proliferation of Hypopharyngeal Carcinoma