| 1996 |
p300 and CBP possess intrinsic histone acetyltransferase (HAT) activity, acetylating all four core histones in nucleosomes, establishing them as a novel class of acetyltransferases lacking the conserved motif found in other acetyltransferases. |
In vitro acetyltransferase assay with recombinant p300/CBP and nucleosomal substrates |
Cell |
High |
8945521
|
| 1994 |
p300 was molecularly cloned and characterized as a transcriptional adaptor protein; it contains a bromodomain and three cysteine/histidine-rich regions, with the C-terminal region binding adenoviral E1A; p300 can overcome E1A repression of the SV40 enhancer, functioning as a transcriptional coactivator. The EP300 gene was mapped to chromosome 22q13. |
cDNA cloning, domain mapping, functional reporter assays |
Genes & development |
High |
7523245
|
| 1996 |
p300 associates with the estrogen receptor (ER) in an agonist-dependent manner and augments ligand-dependent transcriptional activation by ER; p300 is recruited as part of an ER coactivator complex involving ERAP160/SRC1, acting as a point of integration between ER and cAMP signaling pathways. |
Co-immunoprecipitation, ligand-dependent binding assays, transcriptional reporter assays |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
8876171
|
| 1997 |
p300 directly acetylates p53 at its C-terminal regulatory domain (Lys-382), dramatically stimulating p53 sequence-specific DNA-binding activity, likely via acetylation-induced conformational change; this represents the first example of acetylation regulating a non-histone transcription factor. |
In vitro acetyltransferase assay, site-directed mutagenesis, electrophoretic mobility shift assay (EMSA), in vivo acetylation assay |
Cell |
High |
9288740
|
| 1997 |
p300/CBP binds directly to p53 in the absence of viral oncoproteins; p300 and p53 colocalize in the nucleus and coexist in a stable DNA-binding complex; E1A disrupts this complex and suppresses p53-mediated activation of p21/bax promoters and p53-induced cell-cycle arrest and apoptosis. p300/CBP functions as a transcriptional adaptor for p53 in G1 checkpoint control. |
Co-immunoprecipitation, co-localization by immunofluorescence, reporter gene assays, cell-cycle analysis |
Nature |
High |
9194565
|
| 1997 |
p300/CBP physically interact with Smads 1-4 (TGF-β pathway mediators); wild-type E1A, but not p300-binding-deficient E1A mutants, inhibits SMAD-dependent transcriptional responses to TGF-β and Smad4 MH2 domain intrinsic transactivation; overexpression of p300 enhances SMAD-dependent transactivation. |
Co-immunoprecipitation, E1A mutant epistasis, transcriptional reporter assays |
The Journal of biological chemistry |
High |
9722503
|
| 1997 |
MyoD interacts directly with p300/CBP and PCAF, forming a multimeric complex on muscle promoter elements; p300 overexpression promotes p21 expression and terminal cell-cycle arrest, but this activity depends on PCAF's HAT activity rather than p300's. Viral transforming factors disrupt the complex without affecting MyoD-DNA interaction. |
Protein interaction assays (Co-IP, pulldown), reporter assays, antibody microinjection, cell differentiation assays |
Molecular cell |
High |
9659901
|
| 1997 |
C/EBPβ interacts directly with p300; E1A inhibition of C/EBPβ-dependent transactivation requires E1A's p300-binding domain; the interaction maps to the E1A-binding region of p300 and the amino terminus of C/EBPβ; p300 mediates cooperation between C/EBPβ and Myb, revealing a scaffolding role for p300 in transcription factor synergy. |
Co-immunoprecipitation, pulldown assays, reporter gene assays with E1A mutants, dominant-negative inhibition |
Molecular and cellular biology |
High |
9343424
|
| 1998 |
DNA damage triggers p53 acetylation in vivo at Lys-382 by p300, and at Lys-320 by PCAF; N-terminal phosphorylation of p53 (at Ser-33, Ser-37) directs C-terminal acetylation; this phosphorylation-acetylation cascade enhances p53 sequence-specific DNA binding and transcriptional activity. |
In vitro acetyltransferase assay, phospho-specific and acetyl-specific antibodies, UV/IR treatment of cells, mutagenesis |
Genes & development |
High |
9744860
|
| 1999 |
p300 forms a physical and functional bridge between STAT3 and Smad1 in fetal brain; p300 interacts with STAT3 at its N-terminus (cytokine-independent) and with Smad1 at its C-terminus (cytokine-dependent); this STAT3-p300-Smad1 complex mediates cooperative LIF+BMP2 signaling to induce astrocyte differentiation from neural progenitors. |
Co-immunoprecipitation, domain mapping, cell-based differentiation assays |
Science |
High |
10205054
|
| 1999 |
Smad1 interacts with p300 and CBP both in vitro and in vivo via two C-terminal interaction domains binding to a region near the C-terminus of p300/CBP; phosphorylation of Smad1 enhances CBP binding and further stimulates Smad1-dependent transcription; Smad1 N- and C-termini negatively interfere with p300/CBP binding. |
In vitro pulldown, co-immunoprecipitation, domain mapping, transcriptional reporter assays |
Biochimica et biophysica acta |
Medium |
10673036
|
| 2000 |
p300/CBP physically associate with BRCA1 in a phosphorylation-independent manner; BRCA1 interacts with the CREB domain of p300/CBP via both its N- and C-termini; p300/CBP enhance BRCA1-mediated transactivation and this is suppressed by E1A; BRCA1 and p300 associate in a cell cycle-dependent manner by immunocolocalization. |
Co-immunoprecipitation, pulldown assays, reporter gene assays, immunofluorescence co-localization |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
10655477
|
| 2000 |
p300/CBP acetylates MyoD at two lysines at the boundary of the DNA-binding domain; MyoD acetylation by CBP/p300 (and PCAF) increases its transcriptional activity on muscle-specific promoters; MyoD mutants that cannot be acetylated in vitro are not functionally activated. |
In vitro acetyltransferase assay, site-directed mutagenesis, microinjection functional assay |
The Journal of biological chemistry |
High |
10944526
|
| 2000 |
EID-1, a novel Rb-binding protein, binds and inhibits p300's histone acetylase activity, thereby repressing MyoD-mediated skeletal muscle transcription in a manner potentiated by loss of EID-1's Rb binding; this defines p300 HAT activity as essential for MyoD coactivation. |
Yeast two-hybrid, Co-IP, HAT activity assay, reporter gene assays |
Molecular and cellular biology |
Medium |
11073990
|
| 2000 |
Protein kinase C phosphorylates p300 at serine 89 in vivo; this phosphorylation event represses the transcriptional activity of p300, establishing a PKC-regulated signal transduction pathway for p300 function control. |
In vitro kinase assay, in vivo phosphorylation mapping, site-directed mutagenesis, transcriptional reporter assays |
The Journal of biological chemistry |
Medium |
11020388
|
| 2001 |
CBP/p300 HAT activity is required for myogenic terminal differentiation (specifically cell fusion and muscle-specific gene expression) as demonstrated by chemical inhibition of CBP/p300 HAT activity and expression of a transdominant negative HAT mutant. |
Chemical HAT inhibitor, dominant-negative mutant expression, cell differentiation assays |
The EMBO journal |
High |
11726517
|
| 2001 |
MEKK1 enhances p300-mediated transcription by activating multiple domains within p300; p300 is required for MEKK1-induced apoptosis; MEKK1-dependent activation of p300 may involve direct phosphorylation of p300 or non-JNK downstream kinases. |
Reporter gene assays, kinase assays, dominant-negative constructs, apoptosis assays |
The Journal of biological chemistry |
Medium |
11278389
|
| 2001 |
NF-κB RelA subunit is acetylated by CBP/p300; acetylated RelA interacts weakly with IκBα; deacetylation by HDAC3 promotes IκBα binding and CRM1-dependent nuclear export, acting as a molecular switch controlling duration of NF-κB transcriptional response. |
In vitro acetylation assay, Co-IP, nuclear export assays, reporter gene assays |
Science |
High |
11533489
|
| 2002 |
Phosphorylation status of nuclear NF-κB p65 determines its association with either CBP/p300 (phosphorylated p65, transcriptionally active) or HDAC-1 (unphosphorylated p50 homodimers, transcriptionally repressive); only p65 entering nucleus from cytoplasmic NF-κB:IκB complexes can activate transcription through CBP. |
Co-immunoprecipitation, reporter gene assays, chromatin fractionation |
Molecular cell |
High |
11931769
|
| 2002 |
FIH-1 hydroxylates an asparagine residue within the HIF C-terminal transactivation domain under normoxia, blocking its association with p300; under hypoxia, loss of this hydroxylation allows the HIF CAD to interact with p300 and activate transcription. |
In vitro hydroxylase assay, Co-IP, reporter gene assays, mutagenesis |
Genes & development |
High |
12080085
|
| 2002 |
Hydroxylation of a conserved asparagine in the HIF CAD under normoxia prevents interaction with p300; the Fe(II)/2-oxoglutarate-dependent dioxygenase inhibitors block this hydroxylation and constitutively allow HIF CAD-p300 interaction; Asn-to-Ala mutation results in constitutive p300 binding and strong transcriptional activity. |
Mutagenesis, in vitro hydroxylation, Co-IP with p300, reporter gene assays |
Science |
High |
11823643
|
| 2005 |
Sox9 associates with p300 and other transcriptional cofactors; p300 potentiates Sox9-dependent transcription on chromatinized DNA in vitro, associated with histone hyperacetylation; HDAC inhibitor TSA stimulates Sox9-regulated cartilage matrix genes and induces histone acetylation at the Col2a1 enhancer. |
In vitro transcription on chromatinized templates, Co-IP, ChIP assay |
The Journal of biological chemistry |
Medium |
16109717
|
| 2005 |
GCN5 and p300 functionally cooperate during early embryogenesis; GCN5(+/-)p300(+/-) double heterozygous mice show embryonic lethality with developmental stunting and increased apoptosis at E8.5, whereas PCAF(-/-)p300(+/-) mice are normal, demonstrating specific genetic interaction between GCN5 and p300. |
Genetic epistasis in mice (double-heterozygous knockouts), embryo phenotyping, apoptosis assay |
Developmental dynamics |
High |
15937931
|
| 2006 |
ROCK2 is present in the nucleus, physically associates with p300 acetyltransferase in vitro and in cells, co-fractionates with p300 in large nuclear protein complexes, and phosphorylates p300 in vitro; nuclear-restricted constitutively active ROCK2 induces p300 phosphorylation in cells and increases p300 acetyltransferase activity in vitro. |
Co-immunoprecipitation, in vitro kinase assay, gel filtration, immunofluorescence, acetyltransferase activity assay |
The Journal of biological chemistry |
Medium |
16574662
|
| 2008 |
A point mutation in p300 (Y630N, in the KIX domain) disrupts the interaction between p300 and c-Myb, leading to thrombocytosis and megakaryocyte expansion in mice; this establishes that the p300-c-Myb transcriptional regulatory complex plays an indispensable repressive role in megakaryocyte development. |
ENU mutagenesis screen, in vivo mouse genetic model, protein interaction assay, bone marrow transplantation |
Blood |
High |
18684867
|
| 2009 |
p300 and CBP function as cytoplasmic E4 polyubiquitin ligases for p53; their ubiquitin ligase activities are exclusively cytoplasmic (absent from nuclear extracts); CBP deficiency specifically stabilizes cytoplasmic but not nuclear p53; the N-terminal ~616 aa of CBP (including the C/H1-TAZ1 domain) is sufficient for E4 activity and intrinsic E3 autoubiquitination. |
Cell fractionation, in vitro ubiquitin ligase assay, domain deletion analysis, p300/CBP-deficient cell analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
19805293
|
| 2009 |
IL-4 increases CBP/p300 expression and enhances AR-CBP/p300 interaction, recruiting CBP/p300 to androgen-responsive element promoters; p300/CBP acetylates AR in response to IL-4; siRNA knockdown of CBP/p300 abolishes IL-4-mediated AR activation and AR acetylation. |
Western blot, Co-immunoprecipitation, ChIP assay, siRNA knockdown, reporter assays |
The Prostate |
Medium |
18819102
|
| 2009 |
Plumbagin (RTK1) inhibits p300 HAT activity in a non-competitive manner in vivo; it specifically inhibits p300-mediated acetylation of p53 but not PCAF-mediated acetylation; site-directed mutagenesis and docking studies show a hydrogen bond between the hydroxyl group of plumbagin and Lys-1358 in the p300 HAT domain. |
In vitro acetyltransferase assay, site-directed mutagenesis, docking studies, in vivo acetylation assay |
The Journal of biological chemistry |
Medium |
19570987
|
| 2010 |
p300 acetylates tau protein, preventing its degradation; inhibition of p300 with a small molecule promotes tau deacetylation and eliminates pathogenic p-tau; SIRT1 deacetylates tau and its deletion enhances acetylated-tau and p-tau accumulation. |
In vitro acetyltransferase assay, acetyl-specific antibodies, p300 inhibitor treatment, SIRT1 knockout cells |
Neuron |
High |
20869593
|
| 2011 |
Beta-HPV E6 proteins (types 5 and 8) directly interact with p300, blocking the AKT-p300 association; since AKT association is necessary for p300 stability, this leads to proteasomal degradation of p300 in an E6AP-independent manner, with downstream effects on differentiation markers K1, K10, and Involucrin. |
Co-immunoprecipitation, proteasome inhibitor assays, protein stability assays, knockdown experiments |
PLoS pathogens |
Medium |
21901101
|
| 2014 |
CBP, and less efficiently p300, acetylates PCNA at Lys13, 14, 77, and 80 to promote removal of chromatin-bound PCNA and its proteasomal degradation during nucleotide excision repair (NER); mutation of these residues impairs DNA replication and repair, enhances UV sensitivity, and prevents proteolytic degradation of PCNA after DNA damage. |
In vitro acetyltransferase assay, site-directed mutagenesis, protein stability assays, DNA repair assays, UV sensitivity assays |
Nucleic acids research |
High |
24939902
|
| 2014 |
BAG6 regulates nuclear localization of EP300/p300; in the absence of BAG6, EP300 accumulates in the cytoplasm; BAG6 interaction with EP300 occurs in the cytoplasm and promotes nuclear translocation of EP300 during starvation; this controls EP300-dependent acetylation of p53 (nuclear) and ATG proteins (cytoplasmic), thereby regulating autophagy. |
Immunofluorescence, cell fractionation, Co-IP, acetylation assays, autophagy assays in bag6-/- MEFs |
Autophagy |
Medium |
24852146
|
| 2015 |
p300 catalyzes histone crotonylation in addition to acetylation; p300-catalyzed histone crotonylation directly stimulates transcription to a greater degree than histone acetylation; cellular concentrations of crotonyl-CoA regulate histone crotonylation levels and corresponding gene expression. |
In vitro acetyltransferase/crotonyltransferase assay, metabolic perturbation, gene expression analysis, ChIP-seq |
Molecular cell |
High |
25818647
|
| 2015 |
p300 interacts with and acetylates RORγt at Lys81; p300 knockdown downregulates RORγt protein and RORγt-mediated gene expression in Th17 cells; HDAC1 reciprocally interacts with RORγt and reduces its acetylation level, antagonizing p300's effect on IL-17 transcription. |
Co-immunoprecipitation, in vitro acetyltransferase assay, RNAi knockdown, reporter assays |
Scientific reports |
Medium |
26549310
|
| 2015 |
DDX24 interacts with p300, suppressing p300-mediated acetylation of p53; DDX24 knockdown increases p53 acetylation and p53 transcriptional target (p21, PUMA) activation; DDX24 overexpression inhibits p300-p53 interaction; DDX24 knockdown induces p53-dependent cell cycle arrest and senescence. |
Co-immunoprecipitation, acetylation assays, RNAi knockdown, cell cycle analysis |
Oncogene |
Medium |
25867071
|
| 2016 |
p300 deletion (but not CBP deletion) markedly accelerates leukemogenesis in NHD13 MDS mouse models; loss of p300 restores HSPC self-renewal, promotes symmetric self-renewal divisions, decreases apoptosis, and enhances MAPK and JAK/STAT pathway activation, establishing a specific tumor-suppressor role for p300 distinct from CBP. |
Conditional knockout mouse model, colony-forming assays, in vivo transplantation, pathway activation assays |
Leukemia |
High |
27881875
|
| 2017 |
mTORC1 directly phosphorylates p300 at four serine residues in its C-terminal domain; this phosphorylation prevents the catalytic HAT domain from binding the RING domain, eliminating intramolecular autoinhibition; mTORC1-dependent p300 activation suppresses starvation-induced autophagy and activates lipogenesis. |
In vitro kinase assay, domain interaction assay, mutagenesis, co-immunoprecipitation, autophagy and lipogenesis assays |
Molecular cell |
High |
29033323
|
| 2017 |
p300 functions as a lysine 2-hydroxyisobutyryltransferase (Khib), differentially targeting Khib and Kac on distinct lysine sites (only 6 of 149 p300-targeted Khib sites overlap with 693 Kac sites); p300-mediated Khib targets glycolytic enzymes including ENO1; p300 deletion reduces Khib on these sites, decreasing glycolytic enzyme activity, impairing glycolysis, and causing hypersensitivity to glucose-depletion-induced cell death. |
Proteomics, in vitro acetyltransferase assay with 2-hydroxyisobutyryl-CoA, p300 knockout cells, enzymatic activity assay |
Molecular cell |
High |
29775581
|
| 2018 |
Transcription factor dimerization (IRF3 and STAT1 as models) enables trans-autoacetylation of p300 in a highly conserved intrinsically disordered autoinhibitory lysine-rich loop, activating p300; crystal structure of p300 shows the autoinhibitory loop invading the active site of a neighboring HAT domain (snapshot of trans-autoacetylation intermediate); substrate access involves rearrangement of an autoinhibitory RING domain. |
Crystal structure determination, in vitro autoacetylation assay, mutagenesis, transcription factor dimerization assay |
Nature |
High |
30323286
|
| 2018 |
DYRK1A interacts with p300 and CBP (identified by proteomics); DYRK1A overexpression causes hyperphosphorylation of p300/CBP; DYRK1A co-localizes with p300/CBP at enhancers genome-wide; DYRK1A knockdown causes significant loss of H3K27ac at enhancers, suggesting DYRK1A modulates p300/CBP activity at enhancers. |
Proteomics (affinity purification-MS), Co-IP, ChIP-seq, shRNA knockdown, histone modification analysis |
Nucleic acids research |
Medium |
30137413
|
| 2019 |
p300 acetylates AFF1 (a super elongation complex subunit) at a specific site in response to genotoxic stress; AFF1 acetylation reduces its interaction with other SEC components and impairs P-TEFb-mediated CTD phosphorylation of RNA Pol II in vitro and in vivo; reexpression of wild-type but not acetylation-mimic AFF1 restores SEC assembly and target gene expression; p300-mediated AFF1 acetylation is dynamic and correlates with global transcriptional downregulation during genotoxic stress. |
In vitro acetyltransferase assay, site-specific mutagenesis, Co-IP, reporter gene assays, genotoxic stress cellular assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
31611376
|
| 2019 |
EP300 controls enhancer acetylation in germinal center B cells through distinct transcriptional programs from CREBBP; deletion of Ep300 but not Crebbp impairs GC B cell fitness in vivo; combined loss of Crebbp and Ep300 completely abrogates GC formation; CREBBP-mutant DLBCL cells show synthetic lethality with EP300 inhibition. |
Conditional knockout mouse models, ChIP-seq, B cell functional assays, pharmacological inhibition |
Immunity |
High |
31519498
|
| 2019 |
p300 acetylates HPV E2 at K111, and this acetylation is required for recruitment of Topoisomerase 1 to the viral origin and for viral DNA replication; higher levels of P300 (but not CBP) enhance replication with wild-type E2 but not acetylation-defective K111R mutant. |
Functional replication assay, mutagenesis, topoisomerase recruitment assay |
Journal of virology |
Medium |
30651357
|
| 2020 |
p300 physically interacts with NRF2 and interferes with NRF2-KEAP1 complex formation, increasing NRF2 protein abundance, stability, and nuclear localization; the acetyltransferase activity of p300 is indispensable for these stabilizing effects; p300 overexpression protects cells from oxidative stress. |
Co-immunoprecipitation, protein stability assays, localization experiments, acetyltransferase mutant analysis, cell viability assay |
Biochemical and biophysical research communications |
Medium |
32057361
|
| 2020 |
p300 is the predominant H3K27 acetyltransferase in mouse embryonic stem cells; loss of p300 has greater effect on enhancer acetylation than promoter acetylation; distinct gene sets are transcriptionally dysregulated by p300 vs. CBP depletion; p300 depletion stabilizes p53 pathway targets in mESCs. |
ChIP-seq, ATAC-seq, RNA-seq after p300/CBP knockdown in mESCs |
BMC molecular and cell biology |
Medium |
32690000
|
| 2021 |
Short-chain fatty acids propionate and butyrate are converted to their corresponding acyl-CoAs which are used by p300 to catalyze auto-acylation of the autoinhibitory loop, activating p300 for histone/protein acetylation; this mechanism (not HDAC inhibition) accounts for the hyperacetylation induced by these SCFAs. |
Quantitative proteomics of histone modifications, in vitro acetyltransferase assay, metabolic labeling |
eLife |
High |
34677127
|
| 2022 |
EP300 controls the enhancer landscape in MYCN-amplified neuroblastoma by interacting with TFAP2β (a CRC transcription factor), while CBP has a limited role; a PROTAC degrader JQAD1 selectively targets EP300 for CRBN-dependent degradation, causing loss of H3K27ac at CRC enhancers and neuroblastoma apoptosis. |
ChIP-seq, PROTAC-mediated degradation, Co-IP, cell viability assays, in vivo tumor models |
Cancer discovery |
High |
34772733
|
| 2022 |
NUT contains an acidic transcriptional activation domain that binds the TAZ2 domain of p300; NUT-TAZ2 interaction allosterically activates p300 by relieving TAZ2 autoinhibition; cancer mutations interfering with TAZ2 autoinhibition also allosterically activate p300; p300 activation drives acetylation-dependent feed-forward chromatin interactions via bromodomain multivalent acetyl-lysine binding. |
NMR structure, Co-IP, mutagenesis, acetyltransferase activity assay, ChIP-seq |
Nature communications |
High |
36522330
|
| 2022 |
EP300 KIX domain interaction with transcription factors (including MYB) determines its pro-tumorigenic activity in SCLC; Ala627 in EP300 KIX confers higher protein-binding affinity than the equivalent Asp647 in CREBBP KIX, providing molecular basis for EP300-specific KIX-binding partner selectivity; EP300 mutants lacking the acetyltransferase domain accelerate SCLC but complete Ep300 knockout suppresses SCLC. |
Mouse SCLC models, domain deletion analysis, binding affinity measurements, KIX domain blockade |
Science advances |
High |
35171684
|
| 2023 |
Cryo-EM structures of p300/CBP bound to nucleosomes show that p300/CBP recognizes H4 N-terminal tail acetylation (H4NTac) via its bromodomain and contacts DNA minor grooves outside the bromodomain pocket; this directs the catalytic center to non-H4 histone NTs; p300 primarily writes H2BNT acetylation by reading H4NTac, and H2BNTac promotes H2A-H2B dissociation from the nucleosome; p300/CBP can replicate H3-H4 tetramer acetylation epigenetically. |
Cryo-EM structure determination, in vitro acetyltransferase assay, nucleosome remodeling assay |
Nature communications |
High |
37460559
|
| 2023 |
p300 chromatin-binding in live cells depends entirely on combinatorial binding of multiple TF-interaction domains; acetyltransferase activity opposes p300-chromatin association; N-terminal TF-interaction domains regulate acetyltransferase activity; single TF-interaction domains are insufficient for chromatin binding, implying p300 requires multiple simultaneous TF inputs. |
Single-molecule tracking in live cells, systematic domain mutagenesis, chromatin binding assays |
Molecular cell |
High |
38159566
|
| 2023 |
HDAC8 deacetylates EP300, causing its enzymatic inactivation; HDAC8-mediated EP300 inactivation increases H3K27ac and chromatin accessibility at c-Jun binding sites while decreasing binding at MITF sites, driving a neural crest-stem cell transcriptional state and invasive phenotype promoting melanoma brain metastasis. |
ATAC-seq, ChIP-seq, HDAC8 inhibitor/knockout, EP300 acetylation assay |
Nature communications |
High |
38030596
|
| 2023 |
EP300 facilitates human trophoblast differentiation specifically (not CREBBP); EP300 knockdown but not CREBBP knockdown inhibits TSC differentiation into EVT and STB lineages; EP300 knockdown strongly upregulates TGF-α/EGFR signaling, suggesting EP300 facilitates differentiation by suppressing EGFR signaling. |
RNAi knockdown, CRISPR/Cas9 mutagenesis, trophoblast organoid differentiation assays, RNA-seq |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
37406095
|
| 2024 |
p300 nucleus-to-cytoplasm shuttling regulates mTORC1 activity in response to nutrient levels; nutrient depletion triggers AMPK-dependent phosphorylation of p300 at Ser89, causing cytoplasm-to-nucleus relocalization and decreased acetylation of raptor (mTORC1 component), reducing mTORC1 activity and activating autophagy; nutrient readdition causes PP2A-dependent dephosphorylation of nuclear p300 enabling CRM1-dependent nuclear export and mTORC1 reactivation; in Hutchinson-Gilford progeria, progerin mislocalizes p300 causing mTORC1 hyperactivation and defective autophagy. |
Live-cell imaging, cell fractionation, kinase/phosphatase assays, mTORC1 activity assays, AMPK/PP2A inhibitor experiments, CRM1 inhibition, progeria patient cells |
Nature cell biology |
High |
38267537
|
| 2024 |
P300 functions as a histone crotonylation writer during embryonic development; P300 depletion causes developmental defects and transcriptomic dysregulation in embryos; H3K18 crotonylation (H3K18cr) is primarily localized at active promoters and serves as a distinctive epigenetic indicator of transcriptional activation during preimplantation development. |
P300 depletion in embryos, transcriptome analysis, ChIP-seq for H3K18cr, in vitro crotonyltransferase assay |
Nature communications |
High |
39080296
|