The NSL complex maintains nuclear architecture stability via lamin A/C acetylation

Karoutas, Adam; Szymanski, Witold G.; Rausch, Tobias; Guhathakurta, Sukanya; Rog-Zielinska, Eva A.; Peyronnet, Rémi; Seyfferth, Janine; Chen, Huiru; Leeuw, Rebecca de; Herquel, Benjamin; Kimurâ, Hiroshi; Mittler, Gerhard; Kohl, Peter; Medalia, Ohad; Korbel, Jan O.; Akhtar, Asifa

doi:10.1038/s41556-019-0397-z

Cited by 74 publications

(90 citation statements)

References 70 publications

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“…Bioinformatic prediction and experimental verification demonstrated that ITGB1-DT physically bound to EZH2 and competitively reduced the binding of EZH2 to ITGB1 promoter. EZH2 is a well-documented epigenetic regulator, which induces H3K27me3 at target gene promoter and represses target gene expression (Karoutas et al, 2019;Karakashev et al, 2020). Consistently, the binding of ITGB1-DT to EZH2 increased ITGB1 expression by reducing the binding of EZH2 to ITGB1 promoter and H3K27me3 levels at ITGB1 promoter.…”

Section: Discussionmentioning

confidence: 86%

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC

Chang

Xiao

et al. 2021

Front. Cell Dev. Biol.

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Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/β-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/β-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/β-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/β-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD.

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Section: Discussionmentioning

confidence: 86%

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC

Chang

Xiao

et al. 2021

Front. Cell Dev. Biol.

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“…Kansl2 fl/fl mice were generated from mouse embryonic stem cells (mESCs) [tm1a(EUCOMM)Wtsi] obtained from the International Knockout Mouse Consortium ( 54 ) . Kansl3 fl/fl animals were obtained by targeting mESC using a vector obtained from J. Rientjes (Monash, Australia) ( 55 ). Eight- to 12-week-old mice from both sexes were randomly allocated to experimental groups.…”

Section: Methodsmentioning

confidence: 99%

Temporal expression of MOF acetyltransferase primes transcription factor networks for erythroid fate

et al. 2020

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Self-renewal and differentiation of hematopoietic stem cells (HSCs) are orchestrated by the combinatorial action of transcription factors and epigenetic regulators. Here, we have explored the mechanism by which histone H4 lysine 16 acetyltransferase MOF regulates erythropoiesis. Single-cell RNA sequencing and chromatin immunoprecipitation sequencing uncovered that MOF influences erythroid trajectory by dynamic recruitment to chromatin and its haploinsufficiency causes accumulation of a transient HSC population. A regulatory network consisting of MOF, RUNX1, and GFI1B is critical for erythroid fate commitment. GFI1B acts as a Mof activator which is necessary and sufficient for cell type-specific induction of Mof expression. Plasticity of Mof-depleted HSCs can be rescued by expression of a downstream effector, Gata1, or by rebalancing acetylation via a histone deacetylase inhibitor. Accurate timing and dosage of Mof expression act as a rheostat for the feedforward transcription factor network that safeguards progression along the erythroid fate.

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“…Finally, we also evaluated the pathway involvement of the proteins associated with the peptide substrates selected for D-TRAINING. Interestingly, most of the proteins harboring the peptides for which KDAC6 displayed the greatest deacetylase activity (>40,000 M -1 s -1 ) either play a structural role or are associated with cellular structural elements (LMNA [53], MYO1G [54], ACTN1 [55], TUBA1A [8,56,57], have chaperone functions (GRP94 [58], HSP90 [10,11]), or are involved in the Rho signaling pathway (ARHGEF1 [59]).…”

Section: Resultsmentioning

confidence: 99%

Structure-based prediction of HDAC6 substrates validated by enzymatic assay reveals determinants of promiscuity and detects new potential substrates

Jk¹,

Diffley

et al. 2021

Preprint

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Histone deacetylases play important biological roles well beyond the deacetylation of histone tails, and therefore have recently been renamed to acetyl-lysine deacetylases (KDACs). In particular, KDAC6 is involved in multiple cellular processes such as apoptosis, cytoskeleton reorganization, and protein folding, affecting substrates such as α-tubulin, Hsp90 and cortactin proteins. We have applied a biochemical enzymatic assay to measure the activity of KDAC6 on a set of candidate unlabeled peptides. These served for the calibration of a structure-based substrate prediction protocol, Rosetta FlexPepBind, previously used for the successful substrate prediction of KDAC8 and other enzymes. The calibration process and comparison of the results between KDAC6 and KDAC8 highlighted structural differences that explain the already reported promiscuity of KDAC6. A proteome-wide screen of reported acetylation sites using our calibrated protocol together with the enzymatic assay provide new peptide substrates and avenues to novel potential functional regulatory roles of this promiscuous, multi-faceted enzyme.

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The NSL complex maintains nuclear architecture stability via lamin A/C acetylation

Cited by 74 publications

References 70 publications

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC

Temporal expression of MOF acetyltransferase primes transcription factor networks for erythroid fate

Structure-based prediction of HDAC6 substrates validated by enzymatic assay reveals determinants of promiscuity and detects new potential substrates

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