Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Histone PTM analysis in breast cancer cells treated with methyltransferase inhibitors

ABSTRACT: Histone PTM analysis were analyzed in breast cancer cells treated with methyltransferase inhibitors.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Roberta Noberini

LAB HEAD: Tiziana Bonaldi

PROVIDER: PXD064421 | Pride | 2025-08-01

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	HS578t_OICR.zip	Other
	MDA-MB-231OICR.zip	Other
	MDA-MB-231_MI-463_MI-503.zip	Other
	MDAMB231_MI36.zip	Other
	QP_250409_13610R1_6.raw	Raw

Items per page:

1 - 5 of 59

Similar Datasets

Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide

Project description:Histone modifying enzymes depend on the availability of cofactors, with acetyl-CoA being required for lysine acetyltransferase (KAT) activity. The discovery that mitochondrial acyl-CoA producing enzymes are also delivered to the nucleus, suggests that high concentrations of metabolites generated locally may impact acetylation of histones and other nuclear substrates and eventually control gene regulation. Here we show that 2-ketoacid dehydrogenase complexes were stably associated with the Mediator complex in macrophages, thus providing a local supply of acetyl-CoA and increasing the generation of hyper-acetylated histone tails. Nitric oxide (NO), which is produced in large amounts in LPS-stimulated macrophages, inhibited both the activity of 2-ketoacid dehydrogenases and their association with Mediator. Consequently, NO reduced de novo histone acetylation at genomic regions with high acetyl-CoA deposition rates. Our findings indicate that a local supply of acetyl-CoA generated by Mediator-bound 2-ketoacid dehydrogenases is required to maximize acetylation of histone tails at sites of elevated HAT activity.

2024-02-14 | PXD040937 | Pride

Unperturbed dormancy recording reveals stochastic awakening strategies in endocrine treated breast cancer cells

Project description:Hormone dependent breast cancer (HDBC) is the most commonly diagnosed tumor type in women. Adjuvant endocrine therapies (ET) have been the cornerstone in the clinical management of HDBC patients for over forty years. A vast proportion of HDBC patients incur long periods of clinical dormancy following ET, with tumour awakening appearing at a steady pace for up to 25 years (Pan et al., 2017). Extensive genomic studies have demonstrated that 15-30% of clinical relapses develop recurrent genomic changes which contribute to drug resistance (i.e. ESR1 activating mutations) (Bertucci et al., 2019; Magnani et al., 2017; Razavi et al., 2018). However, even in these cases, there is no conclusive evidence around the pre-existence vs. de novo nature of these events. Here, we analyzed histone PTMs in dormant and awakened breast cancer cells treated with endocrine therapy.

2024-05-23 | PXD038030 | Pride

Metabolic and age-associated epigenetic barriers during direct reprogramming of mouse fibroblasts into induced cardiomyocytes

Project description:Heart disease is the leading cause of mortality in developed countries. Although conventional treatments exist, novel regenerative procedures are warranted for improving patients well fare. The use of direct cardiac conversion (DCC) of fibroblasts by the expression of the cardiogenic factors Mef2c, Gata4, and Tbx5 (MGT) can create induced cardiomyocytes (iCMs). Besides holding great promise, DCC lacks clinical effectiveness especially in adult cells, and the impact of metabolic and age-associated epigenetic barriers remains elusive. Here we demonstrate by histone PTMs analysis that DCC triggers major alterations in the epigenetic landscape, which differ with age. Moreover, we show that metabolic modulation in vitro and dietary manipulations in vivo that improves DCC efficiency are accompanied by significant alterations in the histone acetylation and methylation landscape

2025-01-15 | PXD046542 | Pride

Activation of endogenous retroviruses and induction of viral mimicry by MEK1/2 inhibition in pancreatic cancer

Project description:While pancreatic ductal adenocarcinomas (PDAC) are addicted to KRAS-activating mutations, inhibitors of downstream effectors in the KRAS pathway, such as the clinically approved MEK1/2 kinases inhibitor Trametinib, are devoid of significant therapeutic effects. Nevertheless, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway can induce novel functional states and vulnerabilities of potential therapeutic relevance. Here, we performed a quantitative histone post-translatinal modification analysis of PDAC cells in the initial hours after MEK1/2 inhibition by Trametinib.

2024-06-16 | PXD043559 | Pride

Adaptation of the epigenetic regulatory network to the loss of ARID1A and CREBBP

Project description:Epigenetic regulators (ERs) have a central role in regulating gene expression to define cell identity and are amongst the most frequently mutated genes in cancer. However, epigenetic regulators are rarely cell-essential, and in large CRISPR screening projects, human cell lines tolerate the knockout of many key epigenetic regulators with only minor effects on growth. These results indicate that human cells are robust to epigenetic disruption, but how epigenetic pathways interact to form a robust regulatory network is not understood. We are studying the loss of ARID1A and CREBBP, two important ERs that are frequently mutated in multiple cancer types. We analyzed histone post-translational modifications in ARID1A and CREBBP knockout lines in two normal (non-cancerous) human epithelial cell types, HME1 (ATCC, normal human breast epithelia) and HCEC-1CT (Evercyte, normal human colon epithelial).

2025-04-07 | PXD039819 | Pride

Histone PTMs profiles of maltonis treated cells

Project description:The effect of maltonis, a soluble maltol-derived synthetic molecule, on histone PTMs was investigated in NB4 cells.

2023-02-13 | PXD031448 | Pride

Mass spectrometry-based profiling of histone posttranslational modifications in uveal melanoma tissue, human melanocytes, and uveal melanoma cell lines

Project description:Purpose: Epigenetic mechanisms and alterations in uveal melanoma (UM) development are still not well understood. In this pilot study, histone posttranslational modifications (PTMs), which are epigenetic mechanisms regulating gene expression, were analyzed in UM formalin-fixed paraffin-embedded (FFPE) tissues and control tissue as well as in UM cell lines and healthy melanocytes to provide a deeper insight into the pathogenesis of UM and the potentially prognostic relevance of these molecular markers. Methods: FFPE tissue of UM (n=24) and normal choroid (n=4) as well as human UM cell lines (n=7), human skin melanocytes (n=6) and uveal melanocytes (n=2), were analyzed by a quantitative mass spectrometry (MS) approach.

2024-02-14 | PXD043551 | Pride

Multi-acetylated histones are a source of carbon for lipid synthesis

Project description:Histone modifications commonly integrate environmental stimuli to cellular metabolic outputs by affecting gene expression. Many modifications, including some histone acetylation marks, do not always correlate to transcription, thus pointing towards an alternative role of histone modifications as potential metabolic reservoirs. Using an approach that integrates mass spectrometry- based epi-proteomics and metabolomics with stable isotope tracer studies, we demonstrate that elevated lipids in histone acetyltransferase (HAT)-depleted hepatocytes result from carbon atoms flowing from the deacetylation of multi-acetylated histone H4 to fatty acids. Consistent with this, the enhanced lipid synthesis in HAT-depleted hepatocytes is dependent on the activity of histone deacetylases (HDACs) and acetyl-CoA synthetase ACSS2. Furthermore, we show that during diet-induced lipid synthesis there is a reduction of multi-acetylated histone H4 in hepatocytes and in mouse liver. In addition, overexpression of histone acetyltransferases can reverse diet-induced lipogenesis by blocking lipid droplet accumulation and maintaining the levels of multi-acetylated histone H4. This study unveils an additional link between epigenetics and metabolism whereby histone acetylation reservoirs may serve as a carbon source for lipid synthesis.

2024-02-14 | PXD042624 | Pride

Histone PTM profiling in breast cancer clinical samples

Project description:Although cancer was long considered a genetic disease, the contribution of epigenetics to various aspects of cancer biology is now being increasingly recognized. In particular, aberrations in the deposition and maintenance of histone post-translational modifications (PTMs) can result in the inappropriate expression or silencing of genes, potentially leading to cancer. Here, we applied quantitative mass-spectrometry-based technologies to study histone PTMs and variants in different breast cancer subtypes, with a special focus on triple-negative breast cancers (TNBCs), which comprise a heterogeneous group of tumors lacking well-defined molecular targets and targeted therapies.

2025-08-01 | PXD057150 | Pride

Improved Mass Spectrometry-based methods to study histone propionylation

Project description:Histone post-translational modifications (PTMs) have crucial roles in a multitude of cellular processes, their aberrant levels have been linked with numerous diseases, including cancer. Although histone PTM investigations have focused so far on methylations and acetylations, alternative long-chain acylations emerged as new dimension, as they are linked to cellular metabolic states and affect gene expression through mechanisms distinct from those regulated by acetylation. Mass spectrometry (MS) is the most powerful, comprehensive and unbiased method to study histone PTMs. Typical protocols for histone PTM analysis do not allow identification of naturally occurring propionylation and butyrylation. Here, we present improved state-of-the-art sample preparation and analysis protocols to quantitate these classes of modifications. After testing different derivatization methods coupled to protease digestion, we profiled common histone PTMs and histone acylations in seven mouse tissues and human normal and tumor breast clinical samples, obtaining a map of propionylations and butyrylations found in different tissue contexts. A quantitative histone PTM analysis also revealed a contribution of histone acylations in discriminating different tissues and breast cancer samples from the normal counterpart.

2024-07-11 | PXD050362 | Pride