Partners in crime: The role of tandem modules in gene transcription

Sharma, Rajal; Zhou, Ming‐Ming

doi:10.1002/pro.2711

Cited by 12 publications

(13 citation statements)

References 107 publications

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“…To identify the active site in EP300, the three dimensional X ray crystallographic structure of EP300 was downloaded from the Protein Data Bank (http://www.rcsb.org/pdb/home/home.do) (PDB ID: 4BHW) [26]. Therefore, the reported 3D structure of EP300 was applied to docking simulation.…”

Section: Methodsmentioning

confidence: 99%

Tannic acid, a novel histone acetyltransferase inhibitor, prevents non-alcoholic fatty liver disease both in vivo and in vitro model

Chung

Song

Lee

et al. 2019

Molecular Metabolism

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ObjectiveWe examined the potential of tannic acid (TA) as a novel histone acetyltransferase inhibitor (HATi) and demonstrated that TA prevents non-alcoholic fatty liver disease (NAFLD) by inhibiting HAT activity.MethodsThe anti-HAT activity of TA was examined using HAT activity assays. An in vitro NAFLD model was generated by treating HepG2 cells with oleic and palmitic acids. Male C57BL/6J mice were fed a control diet (CD) or Western diet (WD) with or without supplementation with either 1% or 3% TA (w/w) for 12 weeks. Finally, the possibility of interacting p300 and TA was simulated.ResultsTA suppressed HAT activity both in vitro and in vivo. Interestingly, TA abrogated occupancy of p300 on the sterol regulatory element in the fatty acid synthase and ATP-citrate lyase promoters, eventually inducing hypoacetylation of H3K9 and H3K36. Furthermore, TA decreased acetylation at lysine residues 9 and 36 of histone H3 protein and that of total proteins. Consequently, TA decreased the mRNA expression of lipogenesis-related genes and attenuated lipid accumulation in vivo. We observed that NAFLD features, including body weight, liver mass, fat mass, and lipid profile in serum, were improved by TA supplementation in vivo. Finally, we demonstrated the possibility that TA directly binds to p300 through docking simulation between ligand and protein.ConclusionsOur findings demonstrate that TA, a novel HATi, has potential application for the prevention of NAFLD.

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Section: Methodsmentioning

confidence: 99%

Tannic acid, a novel histone acetyltransferase inhibitor, prevents non-alcoholic fatty liver disease both in vivo and in vitro model

Chung

Song

Lee

et al. 2019

Molecular Metabolism

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“…ZMYND function . The ZMYND proteins are part of the bromodomain family 40 and contain conserved C‐terminal MYND domain, PWWP domain, bromodomain and N‐terminal PHD type zinc finger domain; the combination of domains confers the ability to recognise multiple types of histone modification 41 . ZMYND11 forms an oligomer through its C‐terminus; the PHD and MYND domains are important for nuclear localisation and for sumoylation; the PHD domain plays an indispensable role in inhibiting neuronal differentiation 42 .…”

Section: Discussionmentioning

confidence: 99%

ZMYND11 variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder

et al. 2021

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ZMYND11 is the critical gene in chromosome 10p15.3 microdeletion syndrome, a syndromic cause of intellectual disability. The phenotype of ZMYND11 variants has recently been extended to autism and seizures. We expand on the epilepsy phenotype of 20 individuals with pathogenic variants in ZMYND11. We obtained clinical descriptions of 16 new and nine published individuals, plus detailed case history of two children. New individuals were identified through GeneMatcher, ClinVar and the European Network for Therapies in Rare Epilepsy (NETRE). Genetic evaluation was performed using gene panels or exome sequencing; variants were classified using American College of Medical Genetics (ACMG) criteria. Individuals with ZMYND11 associated epilepsy fell into three groups: (i) atypical benign partial epilepsy or idiopathic focal epilepsy (n = 8); (ii) generalised epilepsies/infantile epileptic encephalopathy (n = 4); (iii) unclassified (n = 8). Seizure prognosis ranged from spontaneous remission to drug resistant. Neurodevelopmental deficits were invariable. Dysmorphic features were variable. Variants were distributed across the gene and mostly de novo with no precise genotype–phenotype correlation. ZMYND11 is one of a small group of chromatin reader genes associated in the pathogenesis of epilepsy, and specifically ABPE. More detailed epilepsy descriptions of larger cohorts and functional studies might reveal genotype–phenotype correlation. The epileptogenic mechanism may be linked to interaction with histone H3.3.

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“…[29][30][31] Accordingly, we explored whether linking multiple copies of the CBX1 chromodomain would provide additional improvements beyond a single copy of the eReader. 46 A (GlySer) 10 linker was used to attach three wild-type or engineered CBX1 chromodomains together and the engineered 3x CBX1 eReader was compared to the 3x wild-type CBX1 on peptide arrays (Fig. 5a and b).…”

Section: Multiplexing Of Cbx1 Wild-type or Engineered Chromodomains Show Similar Enhanced H3k9me Recognitionmentioning

confidence: 99%

Engineered Reader Proteins for Enhanced Detection of Methylated Lysine on Histones

et al. 2019

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Histone post-translational modifications (PTMs) are crucial for many cellular processes including mitosis, transcription, and DNA repair. The cellular readout of histone PTMs is dependent on both the chemical modification and histone site, and the array of histone PTMs on chromatin is dynamic throughout the eukaryotic life cycle. Accordingly, methods that report on the presence of PTMs are essential tools for resolving open questions about epigenetic processes and for developing therapeutic diagnostics. Reader domains that recognize histone PTMs have shown potential as advantageous substitutes for anti-PTM antibodies and engineering efforts aimed at enhancing reader domain affinities would advance their efficacy as antibody alternatives. Here we describe engineered chromodomains from D. melanogaster and humans that bind more tightly to H3K9 methylation (H3K9me) marks and result in the tightest reported reader:H3K9me interaction to date. Point mutations near the binding interface of the HP1 chromodomain were screened in a combinatorial fashion, and a triple mutant was found that binds 20-fold tighter than the native scaffold without any loss in PTM-site selectivity. The beneficial mutations were then translated to a human homolog, CBX1, resulting in an even tighter interaction with H3K9me3. Furthermore, we show that these engineered readers (eReaders) increase detection of H3K9me marks in several biochemical assays and outperform a commercial anti-H3K9me antibody in detecting H3K9me-*

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Partners in crime: The role of tandem modules in gene transcription

Cited by 12 publications

References 107 publications

Tannic acid, a novel histone acetyltransferase inhibitor, prevents non-alcoholic fatty liver disease both in vivo and in vitro model

Tannic acid, a novel histone acetyltransferase inhibitor, prevents non-alcoholic fatty liver disease both in vivo and in vitro model

ZMYND11 variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder

Engineered Reader Proteins for Enhanced Detection of Methylated Lysine on Histones

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