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Depletion of TAF1 blocks the proliferation of AE-expressing cells. a–d Knockdown of TAF1 blocks the growth of Kasumi-1 cells (a) and SKNO-1 cells (b) and has little effect on the growth of K562 cells (c) or CD34+ cells (d). Kasumi-1 cells, SKNO-1 cells, K562 cells, and CD34+ cells were infected with scrambled shRNA or TAF1-directed shRNAs. The levels of TAF1 mRNA and TAF1 protein in each type of cells infected with scrambled shRNA or two different TAF1-directed shRNAs are shown in bar graphs and western blots. The TAF1 expression levels after knockdown are indicated as percentage above each column. The cell numbers between cells infected with scrambled shRNA and cells infected with TAF1 shRNAs at last time point were compared using Student t-test. P-values are displayed. e–h Knockdown of TAF1 reduces the percentage of Kasumi-1 cells in the S phase and has no influence on K562 and CD34+ cells. Cells were infected with scrambled shRNA or TAF1 shRNAs for 4 days and subjected for BrdU assay. Representative flow cytometry pictures are shown in e. f–h The percentages of Kasumi-1 cells (f), K562 cells (g), and CD34+ cells (h) with normal or reduced TAF1 levels in the S phase are shown in bar graphs. All experiments were repeated at least two times independently, an = 3, b–d n = 2, fn = 3, g–hn = 2. All error bars represent the mean ± SD. The percentage of cells in the S phase in TAF1 shRNA-infected cells was compared with that in scrambled shRNA-infected cells. P values were determined by Student's t-test. ns represents no significant difference, *p < 0.05, **p < 0.01
Source publication
AML1-ETO (AE) is a fusion transcription factor, generated by the t(8;21) translocation, that functions as a leukemia promoting oncogene. Here, we demonstrate that TATA-Box Binding Protein Associated Factor 1 (TAF1) associates with K43 acetylated AE and this association plays a pivotal role in the proliferation of AE-expressing acute myeloid leukemi...
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Enhancer RNAs (eRNA) are non-coding transcripts produced from active enhancers and have potential gene regulatory function. CCAAT enhancer-binding protein alpha (CEBPA) is a transcription factor generally involved in metabolism, cell cycle inhibition, hematopoiesis, adipogenesis, hepatogenesis, and is associated with tumorigenesis. In this study, w...
Citations
... Western blotting and qPCR analysis indicated that silencing AML1-ETO led to reduced expression of FTO in t(8;21) AML cells (Fig. 1F, G). A similar result was observed in an RNA-seq dataset from GSE115121 in which the expression of AML1-ETO was knocked down in the Kasumi-1 cells [31] (Additional file 1: Fig. S1C). To further determine whether FTO is directly targeted by AML1-ETO, we analyzed a public chromatin immunoprecipitation sequencing (ChIP-seq) dataset that investigated the chromatin occupancy of AML1-ETO in the Kasumi-1 cells (GSE65427) [32]. ...
Background
t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities in acute myeloid leukemia (AML), leading to the generation of the fusion protein AML1-ETO. Despite t(8;21) AML being considered as a subtype with a favorable prognosis, approximately 30–50% of patients experience drug resistance and subsequent relapse. N ⁶ -methyladenosine (m ⁶ A) is demonstrated to be involved in the development of AML. However, the regulatory mechanisms between AML1-ETO and m ⁶ A-related enzymes and the roles of dysregulated m ⁶ A modifications in the t(8;21)-leukemogenesis and chemoresistance remain elusive.
Methods
Chromatin immunoprecipitation, dual-luciferase reporter assay, m ⁶ A-qPCR, RNA immunoprecipitation, and RNA stability assay were used to investigate a regulatory loop between AML1-ETO and FTO, an m ⁶ A demethylase. Gain- and loss-of-function experiments both in vitro and in vivo were further performed. Transcriptome-wide RNA sequencing and m ⁶ A sequencing were conducted to identify the potential targets of FTO.
Results
Here we show that FTO is highly expressed in t(8;21) AML, especially in patients with primary refractory disease. The expression of FTO is positively correlated with AML1-ETO, which is attributed to a positive regulatory loop between the AML1-ETO and FTO. Mechanistically, AML1-ETO upregulates FTO expression through inhibiting the transcriptional repression of FTO mediated by PU.1. Meanwhile, FTO promotes the expression of AML1-ETO by inhibiting YTHDF2-mediated AML1-ETO mRNA decay. Inactivation of FTO significantly suppresses cell proliferation, promotes cell differentiation and renders resistant t(8;21) AML cells sensitive to Ara-C. FTO exerts functions by regulating its mRNA targets, especially IGFBP2, in an m ⁶ A-dependent manner. Regain of Ara-C tolerance is observed when IGFBP2 is overexpressed in FTO-knockdown t(8;21) AML cells.
Conclusion
Our work reveals a therapeutic potential of targeting AML1-ETO/FTO/IGFBP2 minicircuitry in the treatment for t(8;21) patients with resistance to Ara-C.
... The HATs p300/CBP are recruited to the chromatin by binding acetylated E2F1 to further acetylate histone H3 at K14 and K56 positions to initiate DNA repair (23). In another context, the dual bromodomain of TAF1 binds to the AML-ETO fusion transcription factor in an acetylationdependent manner and helps in chromatin localization of AML-ETO in its target genes to promote leukemogenesis (24). ...
Bromodomain-PHD finger protein 1 (BRPF1) belongs to the BRPF family of bromodomain-containing proteins. Bromodomains are exclusive reader modules that recognize and bind acetylated histones and non-histone transcription factors to regulate gene expression. The biological functions of acetylated histone recognition by BRPF1 bromodomain are well characterized; however, the function of BRPF1 regulation via non-histone acetylation is still unexplored. Therefore, identifying the non-histone interactome of BRPF1 is pivotal in deciphering its role in diverse cellular processes, including its misregulation in diseases like cancer. Herein, we identified the non-histone interacting partners of BRPF1 utilizing a protein engineering-based approach. We site-specifically introduced the unnatural photo-cross-linkable amino acid 4-azido-L-phenylalanine into the bromodomain of BRPF1 without altering its ability to recognize acetylated histone proteins. Upon photoirradiation, the engineered BRPF1 generates a reactive nitrene species, cross-linking interacting partners with spatio-temporal precision. We demonstrated the robust cross-linking efficiency of the engineered variant with reported histone ligands of BRPF1 and further used the variant reader to cross-link its interactome. We also characterized novel interacting partners by proteomics, suggesting roles for BRPF1 in diverse cellular processes. BRPF1 interaction with interleukin enhancer–binding factor 3, one of these novel interacting partners, was further validated by isothermal titration calorimetry and co-IP. Lastly, we used publicly available ChIP-seq and RNA-seq datasets to understand the colocalization of BRPF1 and interleukin enhancer–binding factor 3 in regulating gene expression in the context of hepatocellular carcinoma. Together, these results will be crucial for full understanding of the roles of BRPF1 in transcriptional regulation and in the design of small-molecule inhibitors for cancer treatment.
... Nucleosomes in chromatin are composed of DNA wrapped around eight histone proteins (two each of H2A, H2B, H3, and H4 subunits) (22). The N-terminal tail of histones is post-translationally modified via methylation, phosphorylation, acetylation, ubiquitylation, and sumoylation (23), and these epigenetic marks dictate whether the genes are turned on or off. ...
... This is supported by: (i) decreased phosphorylation of the TAF1 S1353A by AMPKα2 compared to WT TAF1, and conversely greater phosphorylation of TAF1 WT compared to TAF1 S1353A mutant in cells expressing constitutively active (CA)-AMPKα2, and (ii) TAF1 phosphorylation at S1353 impaired the TAF1-Pol II interaction, as evidenced by the decreased interaction between the TAF1 S1353D mutant compared to WT TAF1. Our data showing impaired TAF1-Pol II interaction led to down regulation of histone genes' expression, are consistent with TAF1's role as transcription coactivator (16,22 Error bars represent the mean ± SD (n=3). Significance was assessed using two-tailed Student t test. ...
The survival rates for relapsed/refractory acute lymphoblastic leukemia (ALL) remain poor. We and others have reported that ALL cells are vulnerable to conditions inducing energy/ER-stress mediated by AMP-activated protein kinase (AMPK). To identify the target genes directly regulated by AMPKα2, we performed genome-wide RNA-seq and ChIP-seq in CCRF-CEM (T-ALL) cells expressing HA-AMPKα2 (CN2) under normal and energy/metabolic stress conditions. CN2 cells show significantly altered AMPKα2 genomic binding and transcriptomic profile under metabolic stress conditions, including reduced histone gene expression. Proteomic analysis and in vitro kinase assays identified the TATA-Box–Binding Protein–Associated Factor 1 (TAF1) as a novel AMPKα2 substrate that downregulates histone gene transcription in response to energy/metabolic stress. Knockdown and knockout studies demonstrated that both AMPKα2 and TAF1 are required for histone gene expression. Mechanistically, upon activation, AMPKα2 phosphorylates TAF1 at Ser-1353 which impairs TAF1 interaction with RNA polymerase II (Pol II), leading to a compromised state of p-AMPKα2/p-TAF1/Pol II chromatin association and suppression of transcription. This mechanism was also observed in primary ALL cells and in vivo in NSG mice. Consequently, we uncovered a non-canonical function of AMPK that phosphorylates TAF1, both members of a putative chromatin-associated transcription complex that regulate histone gene expression, among others, in response to energy/metabolic stress.
Implications
Fully delineating the protein interactome by which AMPK regulates adaptive survival responses to energy/metabolic stress, either via epigenetic gene regulation or other mechanisms, will allow the rational development of strategies to overcome de novo or acquired resistance in ALL and other cancers.
... Neurodevelopmental defects have been previously observed in taf1 mutants as evidenced by decreased head-to-body and eye-to-body ratios, and measurements of optic tectum size (Kloet et al., 2012). Loss of TAF1 in rats alters the morphology and function of the cerebellum and cerebral cortex, and leads to hypoplasia and loss of Purkinje cells, with behavioral abnormalities paralleling that seen in TAF1/MRSX33 intellectual disability syndrome (Xu et al., 2019). TAF1 has also been linked to Xlinked dystonia parkinsonism, with an alternatively spliced transcript of TAF1 discovered in neurons (Gudmundsson et al., 2019;Grune et al., 2022;Capponi et al., 2021). ...
Intellectual disability is a neurodevelopmental disorder that affects 2-3% of the general population. Syndromic forms of intellectual disability frequently have a genetic basis and are often accompanied by additional developmental anomalies. Pathogenic variants in components of TATA-binding protein associated factors (TAFs) have recently been identified in a subset of patients with intellectual disability, craniofacial hypoplasia, and congenital heart disease. This syndrome has been termed as a TAFopathy and includes mutations in TATA binding protein (TBP), TAF1, TAF2, and TAF6. The underlying mechanism by which TAFopathies give rise to neurodevelopmental, craniofacial, and cardiac abnormalities remains to be defined. Through a forward genetic screen in zebrafish, we have recovered a recessive mutant phenotype characterized by craniofacial hypoplasia, ventricular hypoplasia, heart failure at 96 h post-fertilization and lethality, and show it is caused by a nonsense mutation in taf5. CRISPR/CAS9 mediated gene editing revealed that these defects where phenocopied by mutations in taf1 and taf5. Mechanistically, taf5-/- zebrafish displayed misregulation in metabolic gene expression and metabolism as evidenced by RNA sequencing, respiration assays, and metabolite studies. Collectively, these findings suggest that the TAF complex may contribute to neurologic, craniofacial, and cardiac development through regulation of metabolism.
... Meanwhile, the second bromodomain of the human transcription initiation factor TFIID subunit 1 (TAF1 (2)) is overexpressed in a variety of cancers and plays a significant role in AML1-ETO fusion gene expression [15]. Furthermore, multiple reports indicate the key roles of TAF1 (2) in AML and provide a new theoretical structural framework to develop direct-acting small molecule inhibitors of TAF1(2) as prospective inflammation pathophysiology and cancer therapeutics [16][17][18][19][20]. framework to develop direct-acting small molecule inhibitors of TAF1(2) as pro inflammation pathophysiology and cancer therapeutics [16][17][18][19][20]. ...
... Meanwhile, the second bromodomain of the human transcription initiation factor TFIID subunit 1 (TAF1 (2)) is overexpressed in a variety of cancers and plays a significant role in AML1-ETO fusion gene expression [15]. Furthermore, multiple reports indicate the key roles of TAF1 (2) in AML and provide a new theoretical structural framework to develop direct-acting small molecule inhibitors of TAF1(2) as prospective inflammation pathophysiology and cancer therapeutics [16][17][18][19][20]. framework to develop direct-acting small molecule inhibitors of TAF1(2) as pro inflammation pathophysiology and cancer therapeutics [16][17][18][19][20]. ...
BRD9 and TAF1(2) have been regarded as significant targets of drug design for clinically treating acute myeloid leukemia, malignancies, and inflammatory diseases. In this study, multiple short molecular dynamics simulations combined with the molecular mechanics generalized Born surface area method were employed to investigate the binding selectivity of three ligands, 67B, 67C, and 69G, to BRD9/TAF1(2) with IC50 values of 230/59 nM, 1400/46 nM, and 160/410 nM, respectively. The computed binding free energies from the MM-GBSA method displayed good correlations with that provided by the experimental data. The results indicate that the enthalpic contributions played a critical factor in the selectivity recognition of inhibitors toward BRD9 and TAF1(2), indicating that 67B and 67C could more favorably bind to TAF1(2) than BRD9, while 69G had better selectivity toward BRD9 over TAF1(2). In addition, the residue-based free energy decomposition approach was adopted to calculate the inhibitor–residue interaction spectrum, and the results determined the gatekeeper (Y106 in BRD9 and Y1589 in TAF1(2)) and lipophilic shelf (G43, F44, and F45 in BRD9 and W1526, P1527, and F1528 in TAF1(2)), which could be identified as hotspots for designing efficient selective inhibitors toward BRD9 and TAF1(2). This work is also expected to provide significant theoretical guidance and insightful molecular mechanisms for the rational designs of efficient selective inhibitors targeting BRD9 and TAF1(2).
... Hence, the ability to identify DAC-sensitive patients would aid clinical decision-making and help improve patient response rates. Notably, a single-arm clinical trial revealed that t(8;21) AML is more sensitive to DAC-based chemotherapy than other AML subtypes [8].t(8;21)(q22;q22) is the most common chromosomal translocation in patients with AML, accounting for 10-20% of the total AML cases [9,10]. Derived from the t(8;21) translocation, the AML1-ETO (AE) fusion protein is primarily associated with enhanced self-renewal and impaired hematopoietic stem cell differentiation [10]. ...
... Notably, a single-arm clinical trial revealed that t(8;21) AML is more sensitive to DAC-based chemotherapy than other AML subtypes [8].t(8;21)(q22;q22) is the most common chromosomal translocation in patients with AML, accounting for 10-20% of the total AML cases [9,10]. Derived from the t(8;21) translocation, the AML1-ETO (AE) fusion protein is primarily associated with enhanced self-renewal and impaired hematopoietic stem cell differentiation [10]. However, this fusion protein is also reported to be involved in DNA methylation regulation through the recruitment of DNA methylation transferase [11]. ...
Background
Despite its inconsistent response rate, decitabine, a demethylating agent, is often used as a non-intensive alternative therapeutic agent for acute myeloid leukemia (AML). It has been reported that relapsed/refractory AML patients with t(8;21) translocation achieved better clinical outcomes with a decitabine-based combination regimen than other AML subtypes; however, the mechanisms underlying this phenomenon remain unknown. Herein, the DNA methylation landscape of de novo patients with the t(8;21) translocation was compared with that of patients without the translocation. Moreover, the methylation changes induced by decitabine-based combination regimens in de novo / complete remission paired samples were investigated to elucidate the mechanisms underlying the better responses observed in t(8;21) AML patients treated with decitabine.
Methods
Thirty-three bone marrow samples from 28 non-M3 AML patients were subjected to DNA methylation sequencing to identify the differentially methylated regions and genes of interest. TCGA-AML Genome Atlas-AML transcriptome dataset was used to identify decitabine-sensitive genes that were downregulated following exposure to a decitabine-based regimen. In addition, the effect of decitabine-sensitive gene on cell apoptosis was examined in vitro using Kasumi-1 and SKNO-1 cells.
Results
A total of 1377 differentially methylated regions that specifically responsive to decitabine in t(8;21) AML were identified, of which 210 showed hypomethylation patterns following decitabine treatment aligned with the promoter regions of 72 genes. And the methylation-silencing genes, LIN7A , CEBPA , BASP1 , and EMB were identified as critical decitabine-sensitive genes in t(8;21) AML. Moreover, AML patients with hypermethylated LIN7A and reduced LIN7A expression had poor clinical outcomes. Meanwhile, the downregulation of LIN7A inhibited decitabine/cytarabine combination treatment-induced apoptosis in t(8;21) AML cells in vitro.
Conclusion
The findings of this study suggest that LIN7A is a decitabine-sensitive gene in t(8;21) AML patients that may serve as a prognostic biomarker for decitabine-based therapy.
... AML1-ETO, produced by chromosomal translocation t (8;21), acts as a driving factor in leukemogenesis [2,3]. Additionally, it is also one of the earliest indicators used for prognostic monitoring, and provides a new strategy for therapy [4]. These findings indicate that fusion genes play an important role in leukemia and it is urgent to find a new one for further advancement of disease treatment. ...
To investigate the pathogenesis and the refractory/relapse mechanisms in patients with t(16;21)(p11;q22), we retrospectively analyzed the clinical data of six cases in our hospital and sixty-two cases reported in the literature. Among the patients in our hospital, five cases were diagnosed as acute leukemia, and one was myelodysplastic syndrome evolved to acute myeloid leukemia, harboring TLS/FUS-ERG fusion gene; all the cases were detected t(16;21)(p11;q22) translocation, and five cases showed additional chromosomal abnormalities. We firstly report a novel three-way translocation t(11;16;21)(q13;p11;q22), which may affect the prognosis of leukemia with TLS-ERG fusion gene because this patient shows a more satisfactory treatment effect and deeper remission. And we found patients with TLS-ERG are more likely to have bone and arthrosis pain. Besides, CD56 and CD123 were positive in these cases, which are related to poor prognosis and the character of refractory. Moreover, some gene mutations are involved, and GATA2 and SMAD4 mutations were identified when the disease progressed from myelodysplastic syndrome to leukemia. Among sixty-two patients reported in the literature, valid positive percent of CD56 and CD123 were 81% and 14.3%, respectively. Mutation of the RUNX1 gene was detected in four cases, and one patient had multiple mutations, including BCOR, PLCG1, DIS3, BRAF, JAK2, and JAK3. The prominent feature of leukemia carrying the TLS/FUS-ERG gene is its poor prognosis. The relevant mechanism includes new mutation, jumping translocation, different transcripts, and so on. The mechanism still acquaints scarcely, which requires further study.
... To explore the mechanism of how AML1-ETO functions as either repressor or activator on different target genes, we reasoned that, as a transcription factor capable of recruiting both corepressor (Gelmetti et al., 1998;Lutterbach et al., 1998;Wang et al., 1998) and coactivator (Wang et al., 2011;Shia et al., 2012;Chen et al., 2015;Xu et al., 2019), AML1-ETO's "net" activity on a target gene may be related to the "basal" transcription level conducted by the pre-existing transcription factors and cofactors. In this regard, we set out to compare the AML1-ETO upregulated and downregulated genes for the width of the AML1-ETO binding regions in their promoters, which may roughly reflect the abundance of transcription factors and cofactors in these regions (Kasper et al., 2010). ...
The ETO-family transcriptional corepressors, including ETO, ETO2, and MTGR1, are all involved in leukemia-causing chromosomal translocations. In every case, an ETO-family corepressor acquires a DNA-binding domain (DBD) to form a typical transcription factor—the DBD binds to DNA, while the ETO moiety manifests transcriptional activity. A directly comparative study of these “homologous” fusion transcription factors may clarify their similarities and differences in regulating transcription and leukemogenesis. Here, we performed a side-by-side comparison between AML1-ETO and ETO2-GLIS2, the most common fusion proteins in M2-and M7-subtypes of acute myeloid leukemia, respectively, by inducible expression of them in U937 leukemia cells. We found that, although AML1-ETO and ETO2-GLIS2 can use their own DBDs to bind DNA, they share a large proportion of genome-wide binding regions dependent on other cooperative transcription factors, including the ETS-, bZIP- and bHLH-family proteins. AML1-ETO acts as either transcriptional repressor or activator, whereas ETO2-GLIS2 mainly acts as activator. The repressor-versus-activator functions of AML1-ETO might be determined by the abundance of cooperative transcription factors/cofactors on the target genes. Importantly, AML1-ETO and ETO2-GLIS2 differentially regulate key transcription factors in myeloid differentiation including PU.1 and C/EBPβ. Consequently, AML1-ETO inhibits, but ETO2-GLIS2 facilitates, myeloid differentiation of U937 cells. This function of ETO2-GLIS2 is reminiscent of a similar effect of MLL-AF9 as previously reported. Taken together, this directly comparative study between AML1-ETO and ETO2-GLIS2 in the same cellular context provides insights into context-dependent transcription regulatory mechanisms that may underlie how these seemingly “homologous” fusion transcription factors exert distinct functions to drive different subtypes of leukemia.
... 43 Similarly, the double bromodomain of TAF1 is also reported to bind acetylated non-histone proteins. 40,44 The dual bromodomain of TAF1 binds to the p53 master regulator, diacetylated at lysine 373 and 382 positions. 40 This binding directly recruits TAF1 to the core promoter of the p53-regulated p21 gene and enhances transcription activation. ...
... 40 This binding directly recruits TAF1 to the core promoter of the p53-regulated p21 gene and enhances transcription activation. TAF1 also promotes leukemogenesis by binding to the AML1-ETO (AE) fusion transcription factor through an acetylation site at lysine 43 of AE. 44 These TAF1 and non-histone protein interactions are identified by immunoprecipitation (IP) methods, but some protein−protein interactions are transient and cannot survive the traditional IP methods. 15,16 Moreover, the domain-specific interactome cannot be identified by these techniques. ...
Combinatorial readout of histone post-translational modifications by tandem reader modules mediates crosstalk among different histone modifications. To identify the domain-specific interactome of the tandem reader, we engineered the dual bromodomain of TATA-binding protein-associated factor-1 (TAF1) to carry a photoactivatable unnatural amino acid, 4-azido-L-phenylalanine (AzF), via amber suppressor muta-genesis. Using computational approaches, we modeled the targeted residues of TAF1 with AzF to predict the cross-linking distance between the reactive arylazide and its interacting partner. We developed three photoactivatable TAF1 tandem-bromodomain analogues, viz., Y1403AzF in bromodomain 1 (BD1), W1526AzF in bromodomain 2 (BD2), and Y1403AzF/W1526AzF in both BD1 and BD2. Circular dichroism and a thermal shift assay were used to confirm the structural integrity of the engineered readers. Using the TAF1 tandem-bromodomain analogues, we characterized their histone ligand binding properties by isothermal titration calorimetry and photo-cross-linking experiments. We found that the dual bromodomain of TAF1 independently binds and cross-links to different acetylated histone ligands. We further used the engineered BD1 and BD2 analogues of the TAF1 tandem readers to identify their domain-specific interacting partners at the cellular level. Both BD1 and BD2 independently cross-link to a unique interactome, and importantly, the dual cross-linker carrying TAF1 analogue could capture both BD1-and BD2-specific interactomes. Our work concludes that BD1 and BD2 of the TAF1 tandem reader independently recognize their interacting partners to regulate downstream cellular functions.
... We again measured the number and characteristic of peaks called in CUT&Tag data as compared to ChIP-seq. Since ENCODE does not have H3K27ac ChIP-seq data for Kasumi-1 cells, we identified the high-confidence peaks of published H3K27ac ChIPseq data on the same cell line [42]. While GoPeaks showed an enhanced ability to recall peaks across a range of false positive rates, this may have been at the expense of its precision and recall (Fig. 7a, b; Additional file 1: Fig. S4a, b). ...
... K562 H3K4me3 (ENCODE ID ENCFF885FQN), H3K4me1 (ENCODE ID ENCFF759NWD), and H3K27me3 (EN-CODE ID ENCFF795ZOS) ChIP-seq data was accessed from the ENCODE portal [41,47]. Kasumi-1 H3K27ac (ChIP-Atlas SRX ID SRX4143063 and SRX4143067) ChIP-seq data was accessed from ChIP-Atlas [42,55]. The standards were filtered for peaks with -log 10 (p value) > 10 and adjacent peaks were merged if they were within 1000 bp. ...
... The K562 H3K4me3 (EN-CODE ID ENCFF246IEW), H3K4me1 (ENCODE ID ENCFF590NGQ), and H3K27me3 (ENCODE ID ENCFF795ZOS) ChIP-seq datasets analyzed during the current study are available in ENCODE [41,47,[68][69][70][71]. The Kasumi-1 H3K27ac (ChIP-Atlas SRX ID SRX4143063 and SRX4143067) ChIP-seq data analyzed during the current study is available in ChIP-Atlas [42,55,72,73]. ...
Genome-wide mapping of histone modifications is critical to understanding transcriptional regulation. CUT&Tag is a new method for profiling histone modifications, offering improved sensitivity and decreased cost compared with ChIP-seq. Here, we present GoPeaks, a peak calling method specifically designed for histone modification CUT&Tag data. We compare the performance of GoPeaks against commonly used peak calling algorithms to detect histone modifications that display a range of peak profiles and are frequently used in epigenetic studies. We find that GoPeaks robustly detects genome-wide histone modifications and, notably, identifies a substantial number of H3K27ac peaks with improved sensitivity compared to other standard algorithms.
