PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Histone Acetyltransferases”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1978

Calf liver nuclear N-acetyltransferases. Purification and properties of two enzymes with both spermidine acetyltransferase and histone acetyltransferase activities.

Calf liver contains two nuclear N-acetyltransferases which are separated by chromatography on hydroxylapatite. Both acetyltransferase A and acetyltransferase B will transfer acetate from acetyl-CoA to either histone or spermidine. The same protein catalyzes the reaction with both substrates; this is shown by a constant ratio of spermidine to histone activity over a 5,000-fold purification and identical heat denaturation kinetics for both spermidine and histone acetyltransferase activity with each enzyme. Histone is preferentially acetylated when both acceptors are present. Both enzymes preferentially acetylate polyamines (spermidine, spermine, and diaminodipropylamine) to diamines. Acetyltransferase A acetylates histones in the order: whole histone greater than H4 greater than H2A greater than H3 greater than H2B greater than H1; acetyltransferase B in the order: whole histone greater than H4 = H3 greater than H2A greater than H2B greater than H1. Michaelis constants are 2 X 10(-4)M for spermidine and 9 X 10(-6)M for acetyl-CoA. Acetyltransferase A has a molecular weight of 150,000; acetyltransferase B 175,000. Both enzymes are strongly inhibited by p-chloromercuribenzoate and weakly inhibited by EDTA.

Acetyltransferases↗
PubMed1975

Partial characterization of a histone acetyltransferase from trout testis.

Histone acetyltransferase activity of trout testis was studied both in intact nuclei, and in high salt nuclear extracts. With intact nuclei, the distribution of incorporated [14C]acetate in the various histones was similar to that observed in vivo; the arginine-rich histones H3 and H4 showed the highest specific activities, and lower amounts of label were detected in histones H2a and H2b. Histone H1 incorporated little or no label. Acetyltransferase activity could be detected in purified, sheared chromatin after the addition of MgCl2 or KCl, suggesting that the enzyme is bound to chromatin. Treatment of nuclei with 0.4 M NaCl caused the dissociation of acetyltransferase activity. Most of this solubilized activity failed to bind to DEAE Sephadex and behaved as a high molecular weight heterogeneous complex on Sephadex G-100, suggesting that the enzyme is present as an aggregate with other proteins in the extract. The pH optimum of this preparation was approximately 8.5, and the enzyme showed a preference for histones H3 and H4 as substrates.

Acetates↗
PubMed1979

Purification and properties of a histone acetyltransferase from Artemia salina, highly efficient with H1 histone.

An histone acetyltransferase has been purified from nuclei of 40-h-old Artemia salina larvae. The enzyme is very unstable at 0 degrees C, requires free -SH groups for activity and is rapidly inactivated at 40 degrees C. The optimal pH for activity is 8.5 and the activity is half inhibited by millimolar concentrations of Mn2+, Ca2+ or Mg2+ or decimolar concentrations of Na+ and K+. The molecular weight of the enzyme, determined by gel filtration chromatography, changed with the ionic strength of the medium (280,000 in 10 mM Tris . HCl, 170,000 in 0.2 M KCl). The very-lysine-rich histone H1 is a better substrate acceptor than the arginine-rich histones H3 or H4. Under proper conditions, the enzyme can modify all the internal lysyl residues in histones H1 and H4. The acetylation of H1 is inhibited when all the other histone fractions are present in the assay mixture.

Acetyltransferases↗
PubMed1976

Multiple forms of histone acetyltransferases in the cytosol of calf endometrium.

The histone acetyltransferase (EC 2.3.1.-) activity of calf endometrium cytosol has been separated into three separate activities by stepwise chromatography on DEAE-cellulose. In addition to differential elution from the DEAE-cellulose, the three activities are differentiated by their pH optima, preferences for histone subfractions as substrates, and stability to heat denaturation. Peak I has an optimum of pH 8.7 and preferentially acetylates histones F2b and F3; Peak II has an optimum of pH 8.5, and preferentially acetylates histone F2al followed by histone F2b; Peak III has an optimum of pH 9.5, and had similar specificity to Peak II. Peak III is appreciably more stable at 60 degrees C than is Peak II. None of the peaks transferred acetate to other proteins tested or to tRNA. These studies suggest the presence of multiple histone acetyltransferases in tissue cytosols.

Acetates↗
PubMed2026

ATR-dependent phosphorylation of the histone acetyltransferase HBO1 suppresses chromatin binding and promotes replication stress responses.

Mounting evidence has shown that histone acetyltransferase binding to ORC1 (HBO1) serves as an oncoprotein, warranting the use of the small molecule inhibitor WM-3835 for cancer therapy. However, HBO1 is ubiquitously expressed in both tumor and normal tissues, with potential to increase the risk of systemic toxicity. This unmet need highlights the importance of identifying suitable biomarkers to predict the sensitivity to HBO1 inhibitor. Here, we show that ATR, a key regulator of DNA replication stress, is a novel interacting partner of HBO1. In addition, we reveal a regulatory function of HBO1 in DNA replication stress responses, in an ATR-dependent manner. Mechanistically, ATR mediated HBO1 Ser50/53 phosphorylation interferes with the genomic binding of HBO1 and regulates gene expression. Notably, overexpression of HBO1 mutated at the ATR phosphorylation site (S50/53A) dampens the expression of DNA repair related genes and suppresses tumor colony formation, consistent with the observations of WM-3835 treatment. Inhibition of ATR significantly antagonized the sensitivity to WM-3835 treatment. Collectively, our findings uncovered a previously unidentified role of HBO1 in the regulation of replication stress and discovered ATR as a potential biomarker for WM-3835 treatment.

ATR↗
PubMed2003

Regulation of the bone-specific osteocalcin gene by p300 requires Runx2/Cbfa1 and the vitamin D3 receptor but not p300 intrinsic histone acetyltransferase activity.

p300 is a multifunctional transcriptional coactivator that serves as an adapter for several transcription factors including nuclear steroid hormone receptors. p300 possesses an intrinsic histone acetyltransferase (HAT) activity that may be critical for promoting steroid-dependent transcriptional activation. In osteoblastic cells, transcription of the bone-specific osteocalcin (OC) gene is principally regulated by the Runx2/Cbfa1 transcription factor and is stimulated in response to vitamin D(3) via the vitamin D(3) receptor complex. Therefore, we addressed p300 control of basal and vitamin D(3)-enhanced activity of the OC promoter. We find that transient overexpression of p300 results in a significant dose-dependent increase of both basal and vitamin D(3)-stimulated OC gene activity. This stimulatory effect requires intact Runx2/Cbfa1 binding sites and the vitamin D-responsive element. In addition, by coimmunoprecipitation, we show that the endogenous Runx2/Cbfa1 and p300 proteins are components of the same complexes within osteoblastic cells under physiological concentrations. We also demonstrate by chromatin immunoprecipitation assays that p300, Runx2/Cbfa1, and 1alpha,25-dihydroxyvitamin D(3) receptor interact with the OC promoter in intact osteoblastic cells expressing this gene. The effect of p300 on the OC promoter is independent of its intrinsic HAT activity, as a HAT-deficient p300 mutant protein up-regulates expression and cooperates with P/CAF to the same extent as the wild-type p300. On the basis of these results, we propose that p300 interacts with key transcriptional regulators of the OC gene and bridges distal and proximal OC promoter sequences to facilitate responsiveness to vitamin D(3).

Acetyltransferases↗
PubMed2025

KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia.

UNLABELLED: NUP98 fusion oncoproteins (FO) are a hallmark of childhood acute myeloid leukemia. NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. In this study, we show that MYST family histone acetyltransferase (HAT) complex proteins, including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1, associate with NUP98 FOs on chromatin and within condensates. MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of KAT6A and KAT7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with menin inhibitor treatment, and was efficacious in menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r acute myeloid leukemia. SIGNIFICANCE: KAT6A and KAT7 associate with NUP98 FOs to drive leukemogenesis. Inhibition of their HAT activity is an effective therapeutic strategy in NUP98-r leukemias, including those resistant to menin inhibition. Moreover, combined KAT6A/7 and menin inhibition is synergistic, supporting clinical translation to improve outcomes for NUP98 FO-driven leukemias.

Humans↗
PubMed2025

The pathway of autophagy in the epigenetic landscape of Mycobacterium-host interactions.

Macroautophagy (autophagy) is an evolutionarily conserved process that degrades excess cytoplasmic components, such as protein aggregates and damaged organelles, by encapsulating them within double-membrane autophagosomes. These autophagosomes undergo distinct stages - initiation, phagophore nucleation, expansion, and closure - before fusing with lysosomes (or occasionally endosomes) for degradation and recycling. This process is regulated by ATG (autophagy related) proteins, which govern autophagosome formation and lysosomal fusion. Epigenetic modifications and transcription factors can regulate ATG gene expression in the nucleus. Autophagy also plays a key role in eliminating intracellular Mycobacterium tuberculosis (Mtb) through the lytic and antimicrobial activities of autolysosomes, which are more potent antimicrobial compartments than conventional phagosomes. Emerging evidence suggests that Mtb can modify the host epigenome and transcriptional machinery, significantly affecting the host immune response. This review explores the epigenetic regulation of autophagy during mycobacterium-host interactions. The interplay between epigenetic regulation and autophagy highlights a crucial aspect of host-pathogen interactions during Mtb infection. Understanding how Mtb manipulates the host epigenome to regulate autophagy could lead to the development of novel therapeutic strategies that enhance autophagic pathways or counteract Mtb's immune evasion tactics.Abbreviations: AM: Alveolar macrophages; ATG: autophagy related; DNMT: DNA methyltransferase; FOXO3: forkhead box O3; HAT: histone acetyltransferase; HDAC: histone deacetylase; MIR: microRNA; MTOR: mechanistic target of rapamycin kinase; Mtb: Mycobacterium tuberculosis; ROS: reactive oxygen species; SIRT: sirtuin; STPK: serine/threonine protein kinase.

Autophagy↗
PubMed1977

Acetylation of histones in isolated avian erythroid nuclei.

1. Suspensions of avian erythroid nuclei, of high purity, were prepared. Acetylation of histones was observed when nuclei were incubated in the presence of [1-14C]acetyl CoA, but not in the presence of sodium [3H]acetate. 2. The acetylation reaction was very heat labile and reproduced the in vivo reaction with high fidelity. The reaction was strongly inhibited by divalent cations and cysteine. 3. Studies, in which intact cells were pre-incubated with cycloheximide prior to the isolation of nuclei, suggested that histone acetylation in isolated erythroid nuclei was largely independent of histone synthesis. 4. The pH profile suggested the presence of at least two histone acetyltransferases, with pH optima at 8.0 and 8.6. Acetylation of histone H4 appeared to be favoured at pH 8.0. 5. Studies on histone acetylation in isolated nuclei should be very useful in correlating observations on histone acetylation in vivo, with experiments using purified histone acetyltransferases.

Acetyltransferases↗
PubMed2025

Chromatin remodeling activity of EP400 safeguards chromosomal stability by preventing CENP-A mislocalization.

The mislocalization of CENP-A to non-centromeric regions contributes to chromosomal instability (CIN). The NuA4 histone acetyltransferase complex members EP400 and KAT5 regulate histone H2A.Z-H2B exchange and acetylation of histones, respectively. Overexpression of CENP-A and mutations in NuA4 components are observed in cancers. Here, we define a role for the chromatin remodeling activity of EP400, a top hit in RNAi screens for increased nuclear levels of CENP-A, in preventing CENP-A mislocalization and CIN. Mechanistically, we demonstrate a defect in the extraction of CENP-A from chromatin in cells expressing the EP400K1085G mutant, which lacks ATPase activity for histone exchange. Consistent with these results, EP400K1085G cells show increased CENP-A enrichment in chromatin and mislocalization to non-centromeric regions. Importantly, EP400K1085G cells exhibit CIN phenotypes in stable, near-diploid RPE1 cells with wild-type p53. In summary, our findings expand the role of EP400 from nucleosome destabilization for histone exchange to preventing the stable association of CENP-A with non-centromeric regions and CIN.

Humans↗
PubMed2025

Functions of TIP60/NuA4 Complex Subunits in Cell Differentiation.

The TIP60/NuA4 complex is a large, multifunctional histone acetyltransferase assembly of ~1.7 megadaltons, composed of 17-20 subunits, which plays a central role in epigenetic regulation. Through recognition of H3K4me3 by the ING3 reader, TIP60/NuA4 is recruited to sites of active transcription, where it remodels chromatin to regulate gene expression. Its activities include histone acetylation, histone variant exchange, transcriptional co-activation, and regulation of the cell cycle and apoptosis. In this review, we examine how altered subunit levels or mutations impact the chromatin structure and transcriptional activity, and how these changes influence differentiation across diverse cell types. We emphasize the molecular mechanisms by which TIP60/NuA4 shapes lineage specification, including histone H2A and H4 acetylation by the KAT5 catalytic subunit, H2A.Z incorporation by EP400, and interactions with transcription factors such as MyoD, PPARγ, and Myc. By integrating mechanistic and functional insights, we highlight how TIP60/NuA4 acts as a central epigenetic hub in differentiation and contributes to proper developmental transitions.

Humans↗
PubMed2025

HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury.

Hepatocytes can reprogram into biliary epithelial cells (BECs) during liver injury, but the underlying epigenetic mechanisms remain poorly understood. Here, we define the chromatin dynamics of this process using single-cell ATAC-seq and identify YAP/TEAD activation as a key driver of chromatin remodeling. An in vivo CRISPR screen highlights the histone acetyltransferase HBO1 as a critical barrier to reprogramming. HBO1 is recruited by YAP to target loci, where it promotes histone H3 lysine 14 acetylation (H3K14ac) and engages the chromatin reader zinc-finger MYND-type containing 8 (ZMYND8) to suppress YAP/TEAD-driven transcription. Loss of HBO1 accelerates chromatin remodeling, enhances YAP binding, and enables a more complete hepatocyte-to-BEC transition. Our findings position HBO1 as an epigenetic brake that restrains YAP-mediated reprogramming, suggesting that targeting HBO1 may enhance hepatocyte plasticity for liver regeneration.

Hepatocytes↗
PubMed2003

MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300.

CBP/p300 recruitment to enhancer-bound complexes is a key determinant in promoter activation by many transcription factors. We present a novel mechanism of activating such complexes and show that pre-assembled Elk-1-p300 complexes become activated following Elk-1 phosphorylation by changes in Elk-1-p300 interactions rather than recruitment. It is known that Elk-1 binds to promoter in the absence of stimuli. However, it is unclear how activation of Elk-1 by mitogen-acivated protein kinase (MAPK)-mediated phosphorylation leads to targeted gene transactivation. We show that Elk-1 can interact with p300 in vitro and in vivo in the absence of a stimulus through the Elk-1 C-terminus and the p300 N-terminus. Phosphorylation on Ser383 and Ser389 of Elk-1 by MAPK enhances this basal binding but, most importantly, Elk-1 exhibits new interactions with p300. These interaction changes render a strong histone acetyltransferase activity in the Elk-1-associated complex that could play a critical role in chromatin remodeling and gene activation. The pre-assembly mechanism may greatly accelerate transcription activation, which is important in regulation of expression of immediate-early response genes, in particular those involved in stress responses.

Acetyltransferases↗
PubMed2026

Epigenetic-epitranscriptomic crosstalk through TaHAG1-TaNSUN2 coordinates thermotolerance in wheat.

High temperature is a primary abiotic stress that severely constrains crop productivity. Deciphering the regulatory pathways underlying heat responses is essential for breeding heat-tolerant crops with stable yields. Although both epigenetic and epitranscriptomic regulations are involved in plant heat adaptation, their mechanistic interplay remains unclear. Here, integrated epigenomic (H3K9Ac/H3K14Ac) and transcriptomic profiling under heat stress identifies the mRNA m⁵C methyltransferase TaNSUN2 as a key regulator of thermotolerance in wheat. We demonstrate that TaNSUN2 is transcriptionally activated by the histone acetyltransferase TaHAG1, which deposits H3K9Ac at the TaNSUN2 promoter and transcription start site. This recruitment is facilitated by the transcription factors TaE2F1 and TaDP1, which interact with TaHAG1 to form a functional complex. Functional assays revealthat TaNSUN2 operates downstream of TaHAG1 and enhances thermotolerance through m⁵C‑dependent mRNA methylation and stabilization of transcripts involved in chloroplast organization. Furthermore, field trials show that TaNSUN2-overexpressing lines exhibit higher grain yield under normal conditions and reduced yield loss under heat stress. Our findings elucidate an integrated regulatory network linking histone acetylation to RNA m⁵C methylation in heat stress adaptation, providing promising targets for molecular breeding of heat‑resilient wheat.

Triticum↗