| 1999 |
HBO1 (KAT7) was identified as a novel protein that physically interacts with the human ORC1 subunit of the origin recognition complex. HBO1 exists as part of a multisubunit complex with histone H3 and H4 acetyltransferase activities, and a fraction associates with ORC1 in human cell extracts. |
Yeast two-hybrid screen, co-immunoprecipitation from human cell extracts, in vitro HAT assay |
The Journal of biological chemistry |
High |
10438470
|
| 2001 |
HBO1 directly interacts with MCM2 via its C2HC zinc finger domain. An N-terminal domain of MCM2 is necessary for binding HBO1, and the C2HC zinc finger of HBO1 is essential for MCM2 binding. A suppressor screen in yeast confirmed the interaction is direct and mediated by the zinc finger. |
Yeast two-hybrid, in vitro binding assays, in vivo co-immunoprecipitation, reverse two-hybrid selection, suppressor mutagenesis |
The Journal of biological chemistry |
High |
11278932
|
| 2000 |
HBO1 interacts with the androgen receptor (AR) in a ligand-enhanced manner and acts as a transcriptional repressor of AR-mediated transcription. A transcriptional repression domain was mapped to the N-terminal region of HBO1. HBO1 is localized to the nucleus. |
Yeast two-hybrid, in vitro and in vivo co-immunoprecipitation, immunofluorescence, transient transfection reporter assays, GAL4-DBD mapping |
The Journal of biological chemistry |
Medium |
10930412
|
| 2006 |
Hbo1 is a positive regulatory factor for pre-replication complex (pre-RC) assembly. Depletion of Hbo1 in human cells caused failure of Mcm2-7 to associate with chromatin even though ORC and Cdc6 loading was normal. Immunodepletion of Xenopus Hbo1 from egg extracts abolished MCM loading and DNA replication, which could be rescued by addition of recombinant Cdt1. |
siRNA knockdown in human cells, immunodepletion of Xenopus egg extracts, chromatin fractionation, recombinant protein rescue |
Molecular and cellular biology |
High |
16428461
|
| 2008 |
HBO1 is a coactivator of the replication licensing factor Cdt1. HBO1 associates with replication origins during G1 phase in a Cdt1-dependent manner, directly interacts with Cdt1, and enhances Cdt1-dependent rereplication. This association is independent of the Cdt1 repressor Geminin. |
Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), rereplication assay, cell-cycle fractionation |
Genes & development |
High |
18832067
|
| 2008 |
Plk1 phosphorylates Hbo1 on Ser-57 in vitro and in vivo during mitosis. Cdk1 first phosphorylates Hbo1 on Thr-85/88, creating a docking site for Plk1 recruitment. The Plk1 phosphorylation-defective mutant (S57A) causes G1/S arrest, inhibits MCM chromatin loading, and reduces DNA replication. |
Yeast two-hybrid, in vitro kinase assay, phospho-specific antibodies, cell-cycle analysis, chromatin fractionation, overexpression of phospho-mutants |
Proceedings of the National Academy of Sciences of the United States of America |
High |
18250300
|
| 2008 |
Jade-1/1L is a crucial co-factor that positively regulates HBO1-mediated histone H4 acetylation. PHD fingers of Jade-1/1L are required for nucleosomal H4 acetylation but not for mutual binding. Co-expression of Jade-1/1L and HBO1 synergistically increases H4 acetylation in vivo and in vitro using reconstituted oligonucleosome substrates. |
Co-immunoprecipitation, in vitro HAT assay with oligonucleosome substrates, siRNA depletion, PHD finger deletion mutants, cell-based H4 acetylation assay |
The Journal of biological chemistry |
High |
18684714
|
| 2009 |
HBO1 HAT complexes contain PHD finger domains in ING4/5 and JADE1/2/3 subunits that interact with the histone H3 N-terminal tail with distinct specificities toward its methylation status. Their combinatorial action regulates chromatin binding and substrate specificity of HBO1 complexes. HBO1 complexes are enriched throughout gene coding regions, supporting a role in transcription elongation. |
Biochemical analyses (pulldown, co-IP), genome-wide ChIP analysis, mutant analysis of PHD domains, cell growth assay |
Molecular cell |
High |
19187766
|
| 2009 |
Recombinant Hbo1 acetylates nucleosomal histone H4 in vitro, with a preference for lysines 5 and 12. Hbo1 protein is approximately equimolar with active replication origins in normal human fibroblasts. |
In vitro HAT assay with nucleosomal substrates, semi-quantitative western blot |
Gene |
Medium |
19393168
|
| 2007 |
p53 physically interacts with Hbo1 and negatively regulates its HAT activity in vitro and in cells. Physiological stresses that stabilize p53 (hyperosmotic shock and DNA replication fork arrest) inhibit Hbo1 HAT activity in a p53-dependent manner. Hyperosmotic stress during G1 specifically inhibits MCM2-7 chromatin loading. |
Co-immunoprecipitation, in vitro HAT assay, siRNA knockdown, chromatin fractionation under stress conditions |
Molecular and cellular biology |
High |
17954561
|
| 2010 |
HBO1 HAT activity is essential for DNA replication licensing. A HAT-defective mutant of HBO1 bound at origins cannot load the MCM complex. H4 acetylation at origins is cell-cycle regulated (maximal at G1/S). Geminin inhibits HBO1 acetyltransferase activity in the context of a Cdt1-HBO1 complex and inhibits H4 acetylation and MCM loading in vivo. |
HAT-defective mutant analysis, ChIP, MCM loading assay, cell-cycle synchronization, Geminin overexpression and co-IP |
Molecular cell |
High |
20129055
|
| 2010 |
Cdt1-induced large-scale chromatin decondensation required for MCM recruitment requires HBO1 HAT activity and histone H4 modifications. HDAC11 inhibits Cdt1-induced chromatin unfolding and MCM loading. This process is regulated positively by Cdt1 and HBO1 in G1 and repressed by Geminin-HDAC11 in S phase. |
Live-cell chromatin decondensation imaging, HAT-defective mutant, HDAC11 co-immunoprecipitation, MCM loading assay, cell-cycle analysis |
Cell cycle (Georgetown, Tex.) |
Medium |
20980834
|
| 2010 |
HBO1 is the major source of histone H3K14 acetylation in vivo during embryonic development. Loss of HBO1 caused >90% reduction in H3K14ac with no significant reduction at other histone residues, developmental arrest at the 10-somite stage, and decreased expression of developmental genes. No defects in DNA replication or cell proliferation were observed in primary fibroblasts from mutant embryos. |
Conditional knockout mouse model, quantitative western blot for multiple histone marks, gene expression analysis, cell proliferation assays |
Molecular and cellular biology |
High |
21149574
|
| 2011 |
The Hbo1-Brd1/BRPF2 complex is responsible for global acetylation of H3K14. BRD1 bridges HBO1 and its activator ING4. Depletion of Hbo1 similarly reduces H3K14 acetylation in erythroblasts, and the complex is required for fetal liver erythropoiesis and expression of key erythroid regulator genes including Gata1. |
Brd1-knockout mouse, biochemical co-immunoprecipitation, genome-wide ChIP mapping, western blot for H3K14ac, forced expression rescue |
Blood |
High |
21753189
|
| 2011 |
JNK phosphorylates Cdt1 on threonine 29 in response to nongenotoxic stress, leading to rapid dissociation of HBO1 from replication origins and blocking DNA replication initiation. Simultaneously, JNK phosphorylates Jun (AP-1), increasing HBO1 recruitment to stress-response genes. This reciprocal regulation coordinates replication and transcription responses to stress. |
In vitro kinase assay, phospho-specific antibodies, ChIP, mutation of Thr29, DNA replication assay, cell-cycle analysis |
Molecular cell |
High |
21856198
|
| 2011 |
ING4/5 PHD domain association with HBO1-JADE determines the growth inhibitory function of the complex, linked to tumor suppressor activity. HBO1/ING complexes are a major source of H3 and H4 acetylation in vivo. The p53/p21 pathway is a main transcriptional target regulated directly at the p21/CDKN1A initiation site. |
Molecular dissection of protein domains, co-immunoprecipitation, ChIP, PHD mutant analysis, cell growth assays |
Molecular and cellular biology |
Medium |
22144582
|
| 2012 |
Plk1 phosphorylation of Hbo1 transcriptionally increases cFos expression and consequently elevates MDR1, conferring gemcitabine resistance in pancreatic cancer. Cells expressing Plk1-unphosphorylatable Hbo1 mutants are more sensitive to gemcitabine. |
Phospho-mutant overexpression, gene expression analysis, drug sensitivity assays, xenograft mouse model |
Molecular cancer therapeutics |
Medium |
23188630
|
| 2013 |
Hbo1 is a cyclin E/CDK2 substrate; CDK2 phosphorylates Hbo1 at T88. The low-molecular weight cyclin E (LMW-E)/CDK2 complex phosphorylates Hbo1 at T88 without affecting its HAT activity. Wild-type Hbo1 coexpressed with LMW-E/CDK2 promotes cancer stem-like cell enrichment, whereas the T88A mutant reverses this phenotype. |
Protein microarray, in vitro kinase assay, phospho-mutant analysis, cancer stem cell (CD44hi/CD24lo) flow cytometry, mammosphere formation assay |
Cancer research |
Medium |
23955388
|
| 2013 |
Fbxw15 directly interacts with HBO1 and mediates its ubiquitination at Lys338 and proteasomal degradation in the cytoplasm. Mek1 triggers HBO1 phosphorylation and degradation, and this process requires Fbxw15. Fbxw15-mediated HBO1 depletion reduces H3K14 acetylation and cellular proliferation. |
Co-immunoprecipitation, ubiquitination assay, mass spectrometry (Lys338 site), siRNA knockdown, cell proliferation assay |
The Journal of biological chemistry |
Medium |
23319590
|
| 2013 |
Hbo1 promotes proteasome-dependent degradation of estrogen receptor α (ERα) through lysine 48-linked ubiquitination. The acetyltransferase activity of Hbo1 is linked to its ERα ubiquitination activity. Hbo1 depletion increases ERα expression. |
siRNA knockdown, ubiquitination assay, western blot, K48-linked ubiquitin chain analysis |
Cancer science |
Medium |
24125069
|
| 2015 |
UV damage triggers ATM/ATR-dependent phosphorylation of HBO1 on Ser50 and Ser53, which causes preferential interaction with DDB2 and subsequent ubiquitylation by CRL4DDB2, leading to HBO1 degradation and suppression of cell proliferation. Ser50/53Ala mutants maintain H3K14ac and impair cell-cycle regulation in response to UV. |
Phospho-specific antibodies, co-immunoprecipitation, ubiquitination assay, CRL4DDB2 reconstitution, phospho-mutant analysis, UV survival assay |
Molecular and cellular biology |
High |
26572825
|
| 2015 |
BRPF3 specifically forms a tetrameric complex with HBO1 (not with related acetyltransferases MOZ, MORF, TIP60, or MOF) and this complex specifically acetylates histone H3K14. |
Affinity purification, co-immunoprecipitation, western blot for histone marks, LacZ reporter mouse |
The Journal of biological chemistry |
Medium |
26677226
|
| 2015 |
BRPF3 forms a complex with HBO1 that specifically acetylates histone H3K14. BRPF3 and HBO1 are enriched at ORC1-binding sites and replication origins near TSSs. BRPF3 is required for H3K14ac at selected origins and for efficient CDC45 recruitment (origin activation), but not for MCM2-7 loading, defining a distinct licensing-independent role in origin firing. |
RNAi screen for replication regulators, co-immunoprecipitation, genome-wide ChIP-seq, origin firing assay (CDC45 vs MCM loading by ChIP) |
The EMBO journal |
High |
26620551
|
| 2016 |
KAT7 interacts with the CENP-A assembly factor M18BP1. KAT7 knockout in HeLa cells reduces centromeric CENP-A assembly and increases mitotic chromosome misalignment and micronuclei formation. Tethering KAT7 to an ectopic alphoid DNA site removes H3K9me3 and stimulates CENP-A or H3.3 assembly, antagonizing Suv39h1-mediated heterochromatin invasion. |
Co-immunoprecipitation, CRISPR knockout, immunofluorescence for CENP-A and H3K9me3, tethering assay at ectopic alphoid DNA locus |
Developmental cell |
High |
27270040
|
| 2016 |
KAT7 interacts with the N-terminal domain (NTD) of progesterone receptor (PR) in a ligand-dependent manner via its MYST domain and induces SRC-1-dependent coactivation of PR-mediated transcription. HBO1 also interacts with SRC-1a. In HEK293 cells, HBO1 selectively enhances PRB but not PRA transcriptional activity. |
Yeast two-hybrid, GST pull-down, co-immunoprecipitation, transient transfection reporter assays, immunofluorescence, RT-PCR of endogenous target genes |
Molecular endocrinology (Baltimore, Md.) |
Medium |
16645042
|
| 2017 |
The crystal structure of the HBO1 MYST domain in complex with the N-terminal region of BRPF2 reveals key residues for the HBO1-BRPF2 interaction. The N-terminal region of BRPF2 is sufficient to bind HBO1 and potentiate its HAT activity toward H3K14 (free H3, H4, and nucleosomal H3). |
Crystal structure determination, in vitro HAT assay, mutagenesis of key interface residues, cell biological validation |
Nucleic acids research |
High |
28334966
|
| 2017 |
Phosphorylated HBO1 at CPD (cyclobutane pyrimidine dimer) sites mediates histone acetylation to facilitate XPC recruitment at UV-damaged DNA sites. HBO1 also facilitates accumulation of SNF2H-ACF1 chromatin remodeling complex at CPD sites. HBO1 depletion inhibits CPD repair and sensitizes cells to UV. |
siRNA knockdown, immunofluorescence at UV-damage sites, co-immunoprecipitation with DDB2, epistasis in XP patient-derived cells, UV survival assay |
Nature communications |
High |
28719581
|
| 2017 |
Hbo1 has intrinsic ubiquitin E3 ligase activity toward ERα. Estradiol-17β inhibits this E3 ligase activity in vitro, while hyperactive ERα mutants from metastatic breast cancers are better substrates for Hbo1-mediated ubiquitination. |
In vitro ubiquitination assay, Hbo1 knockdown, western blot |
Proceedings of the Japan Academy. Series B, Physical and biological sciences |
Medium |
28769019
|
| 2018 |
JADE1 physically links the catalytic HBO1 subunit with its histone H3-H4 substrate. JADE1 increases catalytic efficiency of HBO1 acetylation of H3-H4 substrate ~5-fold through an N-terminal 21-residue HBO1- and histone-binding domain. HBO1 also contains an N-terminal histone-binding domain (HBD) that makes additional H3-H4 contacts but does not significantly contribute to overall HAT activity. |
In vitro reconstitution with recombinant proteins, kinetic enzyme assays, JADE1 deletion mapping, in vivo validation by deletion mutants |
The Journal of biological chemistry |
High |
29382722
|
| 2018 |
KAT7 mediates H3K14 and H4 acetylation in intragenic regions of EC-enriched genes including VEGFR-2, contributing to RNA polymerase II binding and VEGFR-2 transcription. KAT7 depletion reduces VEGFR-2 expression and disrupts angiogenic potential. KAT7 inhibition in zebrafish disrupts vessel formation, which is rescued by human KAT7. |
siRNA knockdown, ChIP with tiling array, microarray, KAT7 inhibition in zebrafish embryos, rescue with human KAT7 |
The Journal of biological chemistry |
Medium |
29414790
|
| 2018 |
LPS elevates HBO1 protein stability by upregulating the deubiquitinase USP25, which associates with HBO1 and suppresses its ubiquitination. Stabilized HBO1 then modulates inflammatory gene transcription in THP-1 monocytes. |
Co-immunoprecipitation, ubiquitination assay, siRNA knockdown of USP25, western blot, LPS treatment |
Biochimica et biophysica acta. Gene regulatory mechanisms |
Medium |
30745998
|
| 2019 |
The histone acetyltransferase domain of HBO1 is essential for H3K14 acetylation in AML LSCs. H3K14ac facilitates RNA polymerase II processivity to maintain high expression of HOXA9/HOXA10. A competitive acetyl-CoA analogue inhibitor (WM-3835) inhibits HBO1, recapitulating genetic loss-of-function in AML. |
CRISPR domain screen, quantitative mass spectrometry, H3K14ac ChIP-seq, RNA pol II ChIP-seq, shRNA screen in LSC model, small-molecule inhibitor characterization (competitive kinetics with acetyl-CoA) |
Nature |
High |
31827282
|
| 2019 |
LYAR recruits KAT7 to rDNA loci via BRD2 and BRD4 interactions, resulting in enhanced local acetylation of histone H4 at rDNA, thereby promoting rRNA synthesis. BRD2 is required for KAT7 recruitment; LYAR also binds a BRD4-KAT7 complex that independently promotes H4 and H3 acetylation at rDNA. |
Co-immunoprecipitation, ChIP-qPCR, siRNA knockdown, rRNA synthesis measurement |
Nucleic acids research |
Medium |
31504794
|
| 2019 |
UHRF1 interacts with methylated H3K14 and thereby suppresses H3K14 acetylation by KAT7, leading to transcriptional repression of the tumor suppressor TUSC3 in colon cancer cells. |
Co-immunoprecipitation, ChIP, siRNA knockdown, western blot for H3K14ac |
Oncogene |
Medium |
31582837
|
| 2019 |
Myst2/Kat7 interacts with the tumour suppressor protein Niam (Nuclear Interactor of ARF and Mdm2) in mouse embryonic stem cells, as identified by affinity purification-mass spectrometry. Myst2 forms both H3 and H4 histone acetylation complexes in ESCs similar to those in somatic cells. |
Affinity purification coupled to mass spectrometry (AP-MS) in mouse ESCs |
Scientific reports |
Medium |
28811661
|
| 2020 |
KAT7 knockout in HeLa and 293T human cells demonstrates that HBO1 is essential for all H3K14ac but is dispensable for H4 acetylation and DNA replication in human cells. Loss of HBO1 and H3K14ac secondarily causes near-complete loss of H4 acetylation after 4 weeks. HBO1 loss principally affects cell adhesion genes. |
CRISPR/Cas9 knockout, siRNA knockdown in multiple human cell lines, western blot for multiple histone marks, cell proliferation assay, transcriptomic analysis |
Molecular and cellular biology |
High |
31767635
|
| 2020 |
KAT7 loss in AML cells driven by MLL-X fusions leads to rapid and complete loss of both H3K14ac and H4K12ac, reduced proliferation, apoptosis, and differentiation. Loss of these marks causes BRD4 and AF4 to dissociate from MLL-fusion target gene promoters (MEIS1, PBX3, SENP6), implicating acetylated histones as a platform for MLL-fusion adaptor recruitment. |
Genome-wide CRISPR screen, CRISPR KO, ChIP-seq for histone marks and co-factors, gene expression analysis, differentiation assays |
Leukemia |
High |
32764680
|
| 2020 |
Protein kinase D1 (PKD1) directly interacts with and phosphorylates KAT7 at Thr97 and Thr331. PKD1-mediated phosphorylation enhances KAT7 stability by reducing ubiquitination-mediated degradation. Phospho-defective mutant KAT7-T97/331A attenuates H4 acetylation, MCM2/6 chromatin loading, DNA replication, and cell proliferation. |
Co-immunoprecipitation, in vitro kinase assay, phospho-mutant analysis, ubiquitination assay, chromatin fractionation, BrdU incorporation |
Cell death discovery |
Medium |
33014433
|
| 2021 |
HBO1 is a versatile histone acyltransferase that catalyzes not only histone acetylation but also propionylation, butyrylation, and crotonylation in vivo and in vitro, and does so in a JADE or BRPF scaffold protein-dependent manner. The minimal HBO1/BRPF2 complex accommodates acetyl-CoA, propionyl-CoA, butyryl-CoA, and crotonyl-CoA. HBO1 is the key enzyme for H3K14 acylations at transcription start sites. |
In vitro acylation assays with different acyl-CoA substrates, in vivo acylation by mass spectrometry, genome-wide ChIP for acylation marks, CBP vs HBO1 comparison with KO cells |
Nucleic acids research |
High |
34259319
|
| 2021 |
Leukemic MLL fusion proteins associate with the HBO1 HAT complex through their trithorax homology domain 2 (THD2) via ING4/5 and PHF16 subunits. MLL-ELL particularly depends on this association for leukemic transformation. HBO1 complex promotes loading of the AF4/ENL/P-TEFb (AEP) complex onto target promoters over EAF1 and p53. The NUP98-HBO1 fusion exerts oncogenic properties via interaction with MLL, not its intrinsic HAT activity. |
Co-immunoprecipitation in multiple human cell lines, ChIP, leukemic transformation assay in murine hematopoietic progenitors, domain deletion and HAT-dead mutant analysis |
eLife |
High |
34431785
|
| 2022 |
HBO1 is required for H3K14ac throughout the genome in hematopoietic stem cells (HSCs). Loss of HBO1 causes abnormally high recruitment of quiescent HSCs into the cell cycle, leading to HSC pool exhaustion. HBO1 promotes expression of a transcription factor network (Mpl, Tek, Gfi1b, Egr1, Tal1, Gata2, Erg, Pbx1, Meis1, Hox9) essential for HSC quiescence and self-renewal. |
Conditional KO (Mx1-Cre and Rosa26-CreERT2), competitive transplantation, cell-cycle analysis, H3K14ac ChIP-seq, gene expression analysis |
Blood |
High |
34724565
|
| 2022 |
HBO1 catalyzes lysine benzoylation (Kbz) in mammalian cells, acting as a 'writer' of this modification. At least 77 HBO1-targeted Kbz sites were identified in the benzoylome, including at chromatin-related proteins. |
In vitro benzoylation assay, mass spectrometry-based benzoylome analysis in KO cells, western blot |
iScience |
Medium |
36388951
|
| 2022 |
SIRT1 deacetylates KAT7, activating it. SIRT1 loss leads to hyperacetylation of KAT7 and reduced H4K12ac. Overexpression of a non-acetylatable KAT7 mutant partly rescues SIRT1 loss-induced proliferation defects in T-ALL, establishing a NOTCH1-SIRT1-KAT7 regulatory axis. |
Global acetyl proteomics upon SIRT1 loss, KAT7 non-acetylatable mutant rescue, H4K12ac measurement, gene expression profiling |
Blood cancer discovery |
Medium |
36322781
|
| 2022 |
KAT7 mediates the K525 crotonylation of CANX (calnexin). Loss of KAT7 renders MTORC1 insensitive to leucine deprivation. KAT7-mediated CANX K525 crotonylation is required for lysosomal translocation of CANX and subsequent inhibition of Ragulator activity toward RRAG GTPases during leucine deprivation. |
Cell-free MTORC1 activation system, co-immunoprecipitation, site-specific crotonylation mutagenesis (K525), KAT7 KO, lysosomal fractionation |
Autophagy |
Medium |
35266843
|
| 2022 |
KAT7 is required for optimal expansion of medullary thymic epithelial cells (mTECs) and for expression of AIRE-dependent peripheral tissue genes (PTGs), associated with enhanced chromatin accessibility at PTG loci. TEC-specific Kat7 deletion leads to organ-specific autoimmunity resembling Aire-deficient mice. |
Conditional TEC-specific KO, ATAC-seq for chromatin accessibility, gene expression analysis, histological assessment of autoimmunity |
Science immunology |
High |
35061506
|
| 2023 |
HBO1 functions as a lysine lactyltransferase: it catalyzes the addition of lysine lactylation (Kla) in vitro and intracellularly. E508 is a key site for lactyltransferase activity. HBO1 preferentially catalyzes histone H3K9la. Scaffold proteins JADE1 and BRPF2 promote enzymatic activity for histone Kla. H3K9la at TSSs is required for gene transcription. |
In vitro lactyltransferase assay, E508 mutagenesis, quantitative proteomics of Kla sites in KO cells, site-specific antibodies, CUT&Tag for H3K9la at TSSs |
Nature communications |
High |
38670996
|
| 2023 |
KAT7 is required for neural stem cell plasticity and de novo gene activation. KAT7 and H3K14ac are present at inactive genes, intergenic regions, and in heterochromatin — not only at transcribed genes. KAT7 is not required for continued transcription of already-active genes but is indispensable for activation of repressed genes. Loss of KAT7 abolishes neural stem cell differentiation pathways; re-expression restores developmental potential. |
Conditional KO, H3K14ac ChIP-seq, gene expression profiling, neural stem cell differentiation assays, KAT7 re-expression rescue |
Cell reports |
High |
36641753
|
| 2023 |
Identification of histone lysine acetoacetylation (Kacac) as a novel post-translational modification. HBO1, traditionally an acetyltransferase, also serves as an acetoacetyltransferase, adding acetoacetyl groups to histones. 33 Kacac sites on mammalian histones were identified. |
HPLC co-elution, MS/MS analysis with synthetic peptides, western blot, isotopic labeling, in vitro acetoacetyltransferase assay |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
37382194
|
| 2023 |
HBO1 interacts with SMAD4 and co-binds open chromatin marked by H3K14ac and H3K4me3 in undifferentiated hESCs to maintain pluripotency. Upon BMP4-induced differentiation, HBO1/SMAD4 co-occupy mesoderm gene loci. HBO1-null hESCs fail to respond to TGF-β signaling to maintain pluripotency and cannot form mesendoderm. |
Co-immunoprecipitation, ChIP-seq for HBO1 and SMAD4, conditional KO hESCs, differentiation assays (gastruloids, teratomas) |
Nucleic acids research |
High |
38421638
|
| 2023 |
NLRP11 bridges KAT7 to vimentin, enabling KAT7 to directly acetylate vimentin at Lys104. NLRP11 also induces cytoplasmic localization of KAT7 to facilitate vimentin K104Ac. This acetylation promotes EMT and malignant behavior in lung adenocarcinoma. |
Co-immunoprecipitation, in vitro acetylation assay (KAT7 + vimentin substrate), site-specific K104Q/R mutations, subcellular fractionation, in vivo xenograft |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
37424170
|
| 2023 |
KAT7 acetylates H3K14 to enhance MRAS transcription, activating the MAPK/ERK pathway in colorectal cancer. Re-expression of KAT7, but not an acetyltransferase-deficient mutant, rescues MRAS expression and ERK phosphorylation after KAT7 knockdown. |
shRNA knockdown, CRISPR KO, acetyltransferase-dead mutant rescue, RNA-seq, ChIP-qPCR for H3K14ac at MRAS promoter, ERK phosphorylation western blot |
Theranostics |
Medium |
39816686
|
| 2024 |
The PZP (PHD1-zinc-knuckle-PHD2) domain of JADE engages the nucleosome through binding to histone H3 and DNA, directing the HBO1 complex to chromatin targets. Recognition of unmethylated H3K4 by PZP directs enzymatic activity toward histone H4 acetylation, whereas H3K4 hypermethylation alters histone substrate selectivity. These structural findings were linked to leukemogenesis via the NUP98-JADE2 fusion. |
Structural analysis of PZP domain, genomic binding studies (ChIP-seq), complex assembly in vivo, nucleosome-binding assays, leukemic transformation assay |
Nature structural & molecular biology |
High |
38448574
|
| 2024 |
KAT7 crotonylation at K432 (facilitated by hMOF) competes against its acetylation (regulated by HDAC2) at the same residue upon DNA damage. This competition reduces HBO1 histone acetyltransferase activity, leading to decreased H3K14ac at procentriole formation gene promoters and inhibition of procentriole formation. |
Site-specific K432 crotonylation/acetylation mutants, in vitro HAT assay, co-IP with hMOF/HDAC2, ChIP-qPCR for H3K14ac, procentriole formation assay |
Nature communications |
High |
40064919
|
| 2025 |
KAT7 and KAT6A associate with NUP98 fusion oncoproteins on chromatin and within phase-separated condensates via the common subunit BRPF1. Genetic inactivation or pharmacologic inhibition of KAT7 decreases global H3K23ac, displaces NUP98::HOXA9 from chromatin at the Meis1 locus, and leads to myeloid differentiation. KAT6A/7 inhibition is efficacious in menin inhibitor-resistant NUP98-rearranged leukemia. |
CRISPR genetic inactivation, pharmacologic inhibition, ChIP-seq for H3K23ac and NUP98 fusion, co-IP, in vivo xenograft mouse models, synergy analysis with menin inhibitor |
Cancer discovery |
High |
40536430
|
| 2025 |
Loss of KAT7 suppresses KAT7-mediated acetylation of the transcriptional repressor RFX1, stabilizing RFX1 (by blocking its proteasomal degradation) and thereby suppressing FGF1 transcription, leading to neuronal damage. NgBR regulates this axis by controlling KAT7 expression. |
RNA sequencing, co-immunoprecipitation (KAT7-RFX1 interaction), KAT7 KO, western blot for RFX1 stability, FGF1 transcription analysis, neuronal apoptosis assay |
Cellular and molecular life sciences : CMLS |
Medium |
40192836
|
| 2024 |
KAT7 acetylates LDHA at lysine 118 in head and neck squamous carcinoma (HNSCC), enhancing LDHA activity and upregulating LDHA protein expression, thereby promoting the Warburg effect and tumor proliferation/metastasis. |
Co-immunoprecipitation, in vitro acetylation assay, site-specific K118 mutation, lactate production assay, KAT7 KO/OE with LDHA rescue, xenograft mouse model |
Cancer letters |
Medium |
38593918
|
| 2020 |
MEAF6 modulates KAT7 complex assembly; in the absence of MEAF6, KAT7 increases its ability to interact with PHD-finger proteins (Brpfs/Jades). MEAF6 is essential for cell proliferation but not for HAT activity itself. |
Inducible Meaf6 KO in mouse ES cells, co-immunoprecipitation, histone acetylation western blot, cell proliferation assay |
Experimental cell research |
Medium |
32918898
|
| 2020 |
BRPF3-mediated degradation pathway: the E3 ligase HUWE1 mediates ubiquitin-dependent degradation of Myst2/KAT7, and BRPF3 antagonizes HUWE1-mediated Myst2 degradation by direct protein-protein interaction, retaining Myst2 stability. This balance is required for normal differentiation and cell-cycle progression in embryonic stem cells. |
Co-immunoprecipitation, ubiquitination assay, BRPF3/HUWE1 overexpression/KD, Myst2 stability western blot, ESC differentiation assay |
Cell death and differentiation |
Medium |
32555450
|
| 2006 |
HBO1 inhibits NF-κB activity by coactivator sequestration (squelching), not by binding p65/RelA or disrupting NF-κB DNA binding. The N-terminal serine-rich region of HBO1 (not its acetyltransferase domain) is required for this inhibitory activity. |
Reporter gene assay, EMSA, NF-κB component overexpression, N-terminal deletion mutants |
Biochemical and biophysical research communications |
Medium |
16997280
|
| 2007 |
FAD24 interacts with HBO1 and recruits it to origins of DNA replication during late mitosis (when the pre-RC is assembled). When fad24 is knocked down, recruitment of HBO1 to origins is reduced, impairing mitotic clonal expansion during adipogenesis. |
Co-immunoprecipitation, ChIP at replication origins, siRNA knockdown, colocalization by immunofluorescence |
The Journal of biological chemistry |
Medium |
18029353
|
| 2021 |
HBO1 promotes angiogenic tip cell sprouting through maintaining H3K14ac and appropriate gene expression in endothelial cells. Loss of HBO1 impairs developmental sprouting angiogenesis; single-cell RNA-seq reveals increased tip cell abundance and overcrowding in the sprouting front. |
Endothelial-specific conditional KO, retinal wholemount imaging, single-cell RNA-seq, H3K14ac ChIP-seq |
Development (Cambridge, England) |
High |
34550360
|