| 1998 |
C. elegans lin-53 encodes a protein similar to RbAp48 and antagonizes Ras signaling in vulval precursor cells; lin-53 and lin-35 (Rb homolog) act in the same synthetic multivulva pathway to repress transcription of genes required for vulval cell fate expression. |
Genetic epistasis, loss-of-function mutant analysis, sequence homology |
Cell |
High |
9875852
|
| 1998 |
Drosophila p55 (NURF55, ortholog of RbAp48) is an integral subunit of both the NURF chromatin remodeling complex and the CAF-1 chromatin assembly factor, suggesting it functions as a common platform for chromatin metabolism complexes; immunological studies confirm chromosomal association. |
Peptide sequencing, cDNA cloning, immunoprecipitation, immunostaining of polytene chromosomes |
Proceedings of the National Academy of Sciences of the United States of America |
High |
9419341
|
| 1998 |
Purified recombinant RbAp48 binds 3–4 zinc ions per molecule, with binding activity present in both N- and C-terminal halves, suggesting metal binding is an intrinsic property of the WD-40 propeller structure that may mediate protein-protein interactions. |
Metal affinity chromatography, zinc blotting, atomic absorption analysis, metal competition assays |
FEBS letters |
Medium |
9872415
|
| 1999 |
In Xenopus oocytes, RPD3 (HDAC) associates with RbAp48 through N- and C-terminal contacts; RbAp48 also interacts with SIN3; RbAp48 selectively binds the N-terminal tail proximal to the histone fold domain of histone H4 in vivo; RPD3 may be targeted to histones through RbAp48 to direct transcriptional repression. |
Xenopus oocyte microinjection, cofractionation, co-immunoprecipitation, in vivo binding assays, transcriptional repression assays |
Molecular and cellular biology |
High |
10454532
|
| 2000 |
RbAp48 belongs to the Rb-associated histone deacetylase complex; HDAC1 mediates formation of an Rb-RbAp48 ternary complex; cell extracts depleted of RbAp48-containing complexes show reduced deacetylase activity associated with Rb; E2F1 and RbAp48 are physically associated in the presence of Rb and HDAC1. |
Co-immunoprecipitation from live cells, RbAp48 immunodepletion, histone deacetylase activity assay |
The Journal of biological chemistry |
High |
10734134
|
| 2000 |
RbAp48 interacts with a CBP–phospho-CREB complex: CBP from HeLa nuclear extracts co-immunoprecipitates with RbAp48/RbAp46; RbAp48 lowers the Km of CBP histone acetyltransferase activity; RbAp48 facilitates p300-mediated in vitro transcription of a chromatinized template in an acetylCoA-dependent manner; association of core histones and mononucleosomes with the complex is acetylation-dependent. |
Yeast two-hybrid, Co-IP, GST pulldown, in vitro histone acetyltransferase assay (Km measurement), in vitro transcription on chromatinized template |
Molecular and cellular biology |
High |
10866654
|
| 2001 |
HDAC3 physically interacts with RbAp48 both in vitro and in live cells, and recruits RbAp48 to Rb; this interaction is independent of effects on Rb-E2F1 binding; RbAp48 is required for transcriptional repression of E2F activity. |
Co-immunoprecipitation in vivo and in vitro, transcriptional repression assays |
Nucleic acids research |
High |
11470869
|
| 2002 |
Immunoaffinity proteomics of RbAp48 from Jurkat cells identified all known NuRD/Mi-2 complex proteins (including human p66) as interaction partners, plus RNA-binding/pre-mRNA splicing proteins and other novel interactors, suggesting a broader cellular role than previously documented. |
Immunoaffinity purification, capillary HPLC-ion-trap mass spectrometry |
Journal of proteome research |
Medium |
12645902
|
| 2004 |
Drosophila p55 (RbAp48 ortholog) is essential for repression of dE2F2/RBF-regulated target genes in a cell cycle-independent manner; RNAi depletion of p55 derepresses E2F targets regulated by dE2F2/RBF1 and dE2F2/RBF2, but not cell proliferation-coupled E2F targets, indicating distinct repression mechanisms at these two target classes. |
RNAi depletion in Drosophila cells, quantitative RT-PCR of E2F target genes, epistasis analysis |
Molecular and cellular biology |
High |
15456884
|
| 2006 |
RbAp48 overexpression induces p53-mediated apoptosis in exocrine gland cells under estrogen deficiency conditions; apoptosis requires p53 phosphorylation and E2F-1; siRNA knockdown of RbAp48 inhibits this apoptosis; transgenic RbAp48 expression induces apoptosis specifically in exocrine glands. |
Transgenic mouse overexpression, siRNA knockdown, Western blot for p53 phosphorylation, OVX mouse model, genetic knockout (p53−/−, E2F-1−/−, ERα−/−) |
Molecular and cellular biology |
High |
16581768
|
| 2007 |
RbAp48 overexpression induces cytoskeletal reorganization (loss of actin stress fibers, formation of membranous F-actin rings, cell rounding) in breast cancer cells by increasing K-Ras-GTP levels and activating MAPK; pharmacological MAPK inhibition reverses the cytoskeletal changes; RbAp48 knockdown reduces K-Ras activity. |
Transfection/overexpression, siRNA knockdown, Ras activity pulldown (GTP-Ras), pharmacological MAPK inhibition, phalloidin F-actin staining |
Cancer research |
Medium |
17974974
|
| 2010 |
Crystal structure (1.9 Å) of RbAp48 bound to the 15 N-terminal amino acids of FOG-1 reveals that the FOG-1 peptide contacts a negatively charged pocket on top of the RbAp48 β-propeller, distinct from the histone H4-binding surface; RbAp48 interacts with NuRD subunit MTA-1 via a surface distinct from the FOG-binding pocket, establishing how NuRD assembly facilitates cofactor interactions. |
X-ray crystallography (1.9 Å), biochemical binding assays |
The Journal of biological chemistry |
High |
21047798
|
| 2012 |
The H3-H4 histone complex shows structural plasticity that facilitates allosteric exchange between RbAp48 and the histone chaperone ASF1; this exchange has a central role in new nucleosome assembly. |
Biochemical binding/exchange assays, mass spectrometry, EPR (ESR), structural analysis |
Nature structural & molecular biology |
High |
23178455
|
| 2013 |
RbAp48 modifies histone acetylation in the dentate gyrus (DG); dominant-negative inhibition of RbAp48 in young mouse forebrain causes hippocampus-dependent memory deficits and regionally selective decrease in histone acetylation in the DG; RbAp48 up-regulation in aged DG rescues age-related memory loss and histone acetylation abnormalities. |
Transgenic dominant-negative mouse, viral vector overexpression in aged mice, fMRI, novel object recognition, Morris water maze, histone acetylation measurement |
Science translational medicine |
High |
23986399
|
| 2014 |
Crystal structure of RbAp48 in complex with MTA1 shows that RbAp48 binds MTA1 using the same site used to bind histone H4, demonstrating that assembly into NuRD modulates RbAp46/48 interactions with histones; MTA proteins act as scaffolds for NuRD complex assembly; the RbAp48-MTA1 interaction is essential for in vivo integration of RbAp46/48 into NuRD. |
X-ray crystallography, mutagenesis, co-immunoprecipitation to test in vivo integration |
The Journal of biological chemistry |
High |
24920672
|
| 2015 |
Crystal structure of RBBP4 bound to PHF6 peptide (residues 162-170) reveals that PHF6 contacts the top surface of the RBBP4 β-propeller via a positively charged pair of residues inserting into a negatively charged pocket; this pocket overlaps with FOG1 and histone H3 binding but is distinct from histone H4, Su(z)12, and MTA1 sites; PHF6 mutants impairing this interaction reduce PHF6-mediated transcriptional repression in vivo and RBBP4 knockdown diminishes PHF6-mediated repression. |
X-ray crystallography, mutagenesis, Co-IP, transcriptional reporter assay, siRNA knockdown |
The Journal of biological chemistry |
High |
25601084
|
| 2015 |
RBBP4 depletion in mouse oocytes causes hyperacetylation of histones H3K4, H4K8, H4K12, H4K16 during meiosis I, leading to multipolar spindles at metaphase I, chromosome misalignment, and aneuploidy at metaphase II; RBBP4-mediated histone deacetylation promotes bipolar spindle assembly at least partially through Aurora kinase C (AURKC) function. |
siRNA depletion in mouse oocytes, immunofluorescence for spindle assembly, histone acetylation Western blot, chromosome spread analysis |
Biology of reproduction |
High |
25788661
|
| 2015 |
RbAp48 is essential for vertebrate cell viability; conditional knockout in chicken DT40 cells causes delayed S phase, slow DNA synthesis, impaired nascent nucleosome formation, G2/M accumulation, aberrant mitosis with highly condensed chromosomes and chromosome missegregation, dissociation of HP1 from pericentromeric heterochromatin, and elevated H3K9 acetylation with reduced H3K9 methylation. |
Tetracycline-inducible conditional knockout, cell cycle analysis by flow cytometry, BrdU incorporation, chromosome spread, immunostaining for HP1 and histone modifications |
Chromosome research |
High |
26667624
|
| 2016 |
In C. elegans, LIN-53 (RbAp46/48 ortholog) is required for CENP-A(HCP-3) localization to holocentromeres; LIN-53 and CENP-A localizations are interdependent; LIN-53 localizes to the centromere during metaphase in a CENP-A- and M18BP1(KNL-2)-dependent manner; LIN-53 depletion causes anaphase bridges and chromosome missegregation; this centromeric function is independent of histone acetylation, H3K27 trimethylation, or known chromatin-modifying complexes. |
RNAi depletion, immunofluorescence, genetic epistasis with CENP-A and M18BP1 mutants |
Cell reports |
High |
26904949
|
| 2016 |
MTA1 can recruit two copies of RBBP4 simultaneously; negative stain electron microscopy and chemical crosslinking define a low-resolution model of an MTA1-(RBBP4)2 subcomplex. |
Biochemical binding assays, negative stain electron microscopy, chemical crosslinking/mass spectrometry |
Protein science |
Medium |
27144666
|
| 2016 |
RbAp48 binds to the HIV-1 LTR in vitro and represses HIV-1 LTR-mediated basal and activated transcription; ChIP analysis shows RbAp48 occupancy at the HIV-1 LTR in cells; knockdown of RbAp48 promotes HIV infection and virus particle production. |
EMSA, ChIP, siRNA knockdown, HIV-1 LTR-luciferase reporter assay |
International journal of molecular medicine |
Medium |
27222146
|
| 2017 |
Crystal structure of RBBP4 in complex with BCL11A N-terminal peptide (residues 2-16) shows BCL11A contacts the side of the RBBP4 β-propeller via novel interactions distinct from histone H3; BCL11A competes with histone H3 for binding to the negatively charged top face of RBBP4; BCL11A(2-16) pulls down RBBP4, RBBP7, and components of PRC2, NuRD, and SIN3A from cell lysates. |
X-ray crystallography, fluorescence polarization competition assay, GST pulldown from cell lysate |
The Journal of biological chemistry |
High |
29263092
|
| 2018 |
Crystal structure of RBBP4 bound to the N-terminal 14 amino acids of ZNF827 shows RBBP4 forms a negatively charged channel binding ZNF827 through electrostatic interactions; specific RBBP4 residues required for this interaction were identified and mutation prevents RBBP4 binding to both ZNF827 and telomeres, establishing how NuRD is recruited to ALT telomeres via ZNF827. |
X-ray crystallography, mutagenesis, ChIP, Co-IP |
The Biochemical journal |
High |
30045876
|
| 2018 |
RbAp48 controls expression of BDNF and GPR158 (components of osteocalcin signaling) in mouse hippocampus; inhibition of RbAp48 in hippocampal formation blocks OCN's beneficial effects on cognition and causes discrimination memory deficits; disruption of OCN/GPR158 signaling downregulates RbAp48, creating a feedback loop; activation of OCN/GPR158 increases RbAp48 expression in aged DG and rescues age-related memory loss. |
Viral vector RbAp48 inhibition in vivo, GPR158 pharmacological blockade, gene expression analysis, behavioral memory tests |
Cell reports |
Medium |
30355501
|
| 2019 |
LIN-53 (RBBP4/7 ortholog) interacts with the NuRD complex in C. elegans muscles to maintain muscle integrity; LIN-53 also interacts with the SIN3 HDAC complex required for normal lifespan; lin-53 and sin-3 mutants show decreased trehalose levels; trehalose supplementation or enhancement via insulin/IGF1 signaling rescues lifespan defects. |
Genetic mutant analysis, transcriptomics, metabolomics, epistasis with trehalose feeding and insulin pathway |
Aging cell |
Medium |
31397537
|
| 2020 |
RBBP4 loss in mouse embryos causes hyperacetylated histones and severe apoptosis in blastocysts; trophoblast lineage is properly specified but epiblast and primitive endoderm are compromised; RBBP4 is essential for early mouse embryogenesis and inner cell mass formation. |
Conditional knockout mouse, blastocyst outgrowth assay, immunofluorescence for lineage markers and histone acetylation, TUNEL apoptosis assay |
Biology of reproduction |
High |
32285100
|
| 2020 |
Structure-based design of bicyclic peptide inhibitors targeting the RbAp48/MTA1 protein-protein interaction interface achieves nanomolar affinity (KD = 8.56 nM); crystallographic analysis guided affinity optimization via hydrophobic aromatic linker interactions with a hydrophobic residue on RbAp48. |
X-ray crystallography, fluorescence polarization/binding affinity measurement, protease stability assay |
Angewandte Chemie (International ed. in English) |
High |
33022847
|
| 2021 |
Double knockdown of Rbbp4 and Rbbp7 (but not individually) causes embryonic lethality at morula-to-blastocyst transition with cell cycle block, disrupted lineage specification, and a dramatic increase in histone H3.3 and H3K27ac; ChIP-seq shows RBBP4/7 target gene promoters are enriched for H3.3; RBBP4/7 regulate H3.3 deposition epigenetically. |
siRNA double knockdown in mouse embryos, ChIP-seq for H3.3, RNA-seq, immunofluorescence |
Epigenetics |
High |
34709113
|
| 2021 |
RBBP4 deficiency in mouse ESCs causes spontaneous differentiation into mesendodermal lineages; RBBP4 is essential for PRC2 genomic targeting to a subset of developmental genes; RBBP4 sustains Oct4 and Sox2 expression; forced co-expression of Oct4 and Sox2 fully rescues pluripotency in Rbbp4-null ESCs. |
Knockout ESCs, RNA-seq, ChIP-seq for PRC2 components, rescue by Oct4/Sox2 overexpression |
Stem cell reports |
High |
33606987
|
| 2021 |
In Tetrahymena, the RBBP4/7 ortholog RebL1 physically interacts with histone H4 and co-purifies with subunits of CAF1, Hat1, Rpd3, and MuvB complexes; RebL1 is a component of a MuvB-like complex containing Lin54, Lin9, and RebL1; RebL1 and Lin54 bind genic and intergenic regions genome-wide; RebL1 depletion suppresses Rad51 expression, consistent with DNA repair roles. |
Affinity purification/mass spectrometry, ChIP-seq, RNAi depletion, Western blot |
Nucleic acids research |
Medium |
34086947
|
| 2022 |
RBBP4 forms a complex with p300 histone acetyltransferase in the nucleus of GBM cells (demonstrated by proximity ligation assay); ChIP-seq shows co-occupancy of RBBP4/p300 at promoters/enhancers with H3K27ac; RBBP4 and p300 co-regulate 1,485 genes including C-MYC; RBBP4 or p300 knockdown sensitizes GBM cells to temozolomide. |
Proximity ligation assay, ChIP-seq, shRNA knockdown, RNA-seq, in vivo orthotopic tumor model |
Neuro-oncology |
High |
35231103
|
| 2022 |
RBBP4 loss in zebrafish disrupts neural progenitor cell cycle progression independent of Rb1 (rbbp4; rb1 double mutants show additive M-phase accumulation); Rbbp4 loss leads to Tp53 acetylation and Tp53-dependent apoptosis in developing brain; Tp53 knockdown/knockout suppresses apoptosis in rbbp4 mutants. |
Zebrafish genetic mutant analysis (rbbp4, rb1, tp53 mutants), immunofluorescence for γ-H2AX and M-phase markers, epistasis with tp53 morpholino/knockout |
Developmental dynamics |
High |
35266256
|
| 2022 |
Photoaffinity labeling identified RBBP4 as a direct cellular target of protopanaxadiol (PPD) in HCT116 colorectal cancer cells; PPD binding to RBBP4 decreases RBBP4-dependent H3K27me3; PPD inhibition of cell proliferation/migration is antagonized by RBBP4 silencing, confirming RBBP4 as a functional target. |
Photoaffinity labeling chemoproteomic pulldown, H3K27me3 Western blot, siRNA knockdown rescue |
Chembiochem |
Medium |
35442561
|
| 2023 |
RBBP4 recruits transcription factors and epigenetic regulators to the promoters of MRN complex genes (Mre11, Rad50, NBS1) to regulate their expression and thereby controls DNA double-strand break repair; RBBP4 disruption increases DNA damage sensitivity to TMZ and radiotherapy in GBM cells. |
ChIP-seq, shRNA knockdown, γ-H2AX assay, cell proliferation assays |
Cancer letters |
Medium |
36736531
|
| 2023 |
RBBP4 functions as an epigenetic barrier to totipotency: it binds endogenous retroviruses (ERVs) and recruits G9a to deposit H3K9me2 on ERVL elements and recruits KAP1 to deposit H3K9me3 on ERV1/ERVK elements; RBBP4 also facilitates nucleosome occupancy at ERVK/ERVL sites in heterochromatin via chromatin remodeler CHD4; RBBP4 depletion activates transposable elements and 2C genes, reprogramming ESCs toward totipotency. |
Auxin-induced degron depletion, ChIP-seq for H3K9me2/me3 and nucleosome occupancy (ATAC-seq), Co-IP for G9a/KAP1/CHD4, RNA-seq |
Nucleic acids research |
High |
37021556
|
| 2024 |
ZNF512B contains a variant NuRD-interaction motif (NIM) that binds RBBP4; crystal structure of this ZNF512B NIM bound to RBBP4 demonstrates it is necessary and sufficient for high-affinity NuRD binding; ZNF512B recruits NuRD through RBBP4 to repress gene expression. |
X-ray crystallography, biochemical binding assays, mutagenesis, transcriptome analysis, reporter assays |
Nucleic acids research |
High |
39460621
|
| 2024 |
RBBP4 knockdown in mouse E12.5 neocortical progenitors reduces neuronal output, specifically affecting CTIP2-expressing deep-layer neurons; RBBP4 genome-wide occupancy is primarily at distal regulatory elements; RBBP4 binds the Cdon gene (Shh pathway receptor); Cdon knockdown phenocopies RBBP4 knockdown; CDON overexpression rescues neurogenesis defects caused by RBBP4 loss. |
CRISPR/Cas9 knockdown in embryonic neocortex, ChIP-seq, immunofluorescence for neuronal markers, rescue by CDON overexpression |
eNeuro |
High |
39592227
|
| 2025 |
In chronic stress/isoflurane anesthesia cognitive impairment, RbAp48 interacts with HDAC2 (demonstrated by Co-IP); chronic stress reduces RbAp48 expression and increases HDAC2 levels and their interaction, decreasing H3K9ac and H4K12ac; RbAp48 overexpression restores histone acetylation, increases BDNF, and rescues memory deficits. |
Co-immunoprecipitation, Western blot, adenoviral RbAp48 overexpression in vivo and in vitro, fear conditioning behavioral test |
Journal of anesthesia and translational medicine |
Medium |
41930277
|
| 2025 |
RBBP4 knockout in TMZ-resistant glioblastoma cells (identified by CRISPR functional genomic screen using epigenetic knockout library) significantly impairs cell proliferation without affecting MGMT expression; RBBP4 loss downregulates G2/M checkpoint cell cycle genes and causes increased cell size and multinucleation indicative of disrupted mitotic progression. |
CRISPR/Cas9 dropout screen, RNA-seq after RBBP4 KO, live-cell imaging, immunofluorescence |
bioRxivpreprint |
Medium |
|