Summary of Study ST003153

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001959. The data can be accessed directly via it's Project DOI: 10.21228/M8H72Q This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003153
Study TitleUntargeted metabolomic profile in control and YEATS4 knockdown MCF-7 cells
Study SummaryThe integration between epigenetic regulation and metabolism is critical to maintain cellular homeostasis. As an epigenetic mark mainly linked to gene activation, histone crotonylation (Kcr) uses the donor of crotonyl-CoA, a metabolite generated primarily from fatty acid oxidation. Whether there is an intrinsic crosstalk between histone Kcr and fatty acid metabolism remains to be explored. We report here that YEATS family protein YEATS4 is a reader of histone Kcr preferentially towards H3K14cr. YEATS4 is amplified and overexpressed in breast cancer cells, mainly in the ER+ subtype. Integrative epigenomic and transcriptomic analyses reveals extensively overlapped chromatin distribution of YEATS4 with H3K14cr, leading to activation of multiple genes involved in fatty-acid trafficking and metabolism, such as CD36, CPT1/2, and ACOX1. Depletion of YEATS4 in breast cancer cells led to compromised fatty acid uptake and -oxidation. Interestingly, YEATS4 is upregulated in ALDH+ breast cancer stem cells, leading to boosted fatty acid metabolism, enhanced self-renewal, and accelerated tumor growth. Clinicalpathological evidence indicates that elevated YEATS4 expression is correlated with poor prognosis and worse overall survival of ER+ breast cancer patients. Together, our study uncovers a feedforward epigenetic-metabolic loop implicated in breast carcinogenesis, supporting the pursuit of YEATS4 as a potential therapeutic target for breast cancer intervention.
Institute
Peking University
Last NamePeng
First NameZijun
AddressXueyuan Road No.38, Beijing, Bejing, 100191, China
Emailzj_peng@126.com
Phone+86 17317790671
Submit Date2024-03-31
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2025-09-15
Release Version1
Zijun Peng Zijun Peng
https://dx.doi.org/10.21228/M8H72Q
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001959
Project DOI:doi: 10.21228/M8H72Q
Project Title:YEATS4 Links Histone Crotonylation to Fatty-acid Uptake/Metabolism and Breast Cancer Stemness
Project Summary:The integration between epigenetic regulation and metabolism is critical to maintaining cellular homeostasis. As an epigenetic mark mainly linked to gene activation, histone crotonylation (Kcr) uses the donor of crotonyl-CoA, a metabolite generated primarily from fatty acid oxidation. Whether there is an intrinsic crosstalk between histone Kcr and fatty acid metabolism remains to be explored. We report here that the YEATS family protein YEATS4 is a reader of histone Kcr preferentially towards H3K14cr. YEATS4 is amplified and overexpressed in breast cancer cells, mainly in the ER+ subtype. Integrative epigenomic and transcriptomic analyses reveal extensively overlapped chromatin distribution of YEATS4 with H3K14cr, leading to activation of multiple genes involved in fatty acid trafficking and metabolism, such as CD36, CPT1/2, and ACOX1. Depletion of YEATS4 in breast cancer cells led to compromised fatty acid uptake and β-oxidation. Interestingly, YEATS4 is upregulated in ALDH+ breast cancer stem cells, leading to boosted fatty acid metabolism, enhanced self-renewal, and accelerated tumor growth. Clinical pathological evidence indicates that elevated YEATS4 expression is correlated with a poor prognosis and worse overall survival in ER+ breast cancer patients. Together, our study uncovers a feedforward epigenetic-metabolic loop implicated in breast carcinogenesis, supporting the pursuit of YEATS4 as a potential therapeutic target for breast cancer intervention.
Institute:Peking University
Last Name:Peng
First Name:Zijun
Address:Xueyuan Road No.38, Beijing, Bejing, 100191, China
Email:zj_peng@126.com
Phone:+8617317790671

Subject:

Subject ID:SU003270
Subject Type:Cultured cells
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Mammals

Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA341011QC_3quality control
SA341012QC_1quality control
SA341013QC_2quality control
SA340999shNC_6Wild-type
SA341000shNC_1Wild-type
SA341001shNC_5Wild-type
SA341002shNC_4Wild-type
SA341003shNC_3Wild-type
SA341004shNC_2Wild-type
SA341005shYEATS4_1YEATS4 knockdown
SA341006shYEATS4_2YEATS5 knockdown
SA341007shYEATS4_3YEATS6 knockdown
SA341008shYEATS4_4YEATS7 knockdown
SA341009shYEATS4_5YEATS8 knockdown
SA341010shYEATS4_6YEATS9 knockdown
Showing results 1 to 15 of 15

Collection:

Collection ID:CO003263
Collection Summary:Cells were counted, washed with cold PBS and then flash-frozen in liguid N2. Then for each sample, 1000 μL extract solution (acetonitrile: methanol: water = 2: 2: 1) containing the isotopically-labeled internal standard mixture was added. After 30 seconds of vortex, the samples were homogenized at 35 Hz for 4 min and sonicated for 5 min in an ice-water bath. The homogenization and sonication cycle was repeated 2 times. The samples were sonicated for 5 min in an ice-water bath incubated at -40 ℃ for 1 h and centrifuged at 12000 rpm for 15 min at 4°C. 800 μL of supernatant was transferred to a fresh tube and dried in a vacuum concentrator at 37 ℃. Then, the dried samples were reconstituted in 200 μL of 50% acetonitrile by sonication on ice for 10 min. The constitution was then centrifuged at 13000 rpm for 15 min at 4 ℃, and 75 μL of supernatant was transferred to a fresh glass vial for LC/MS analysis. The quality control (QC) sample was prepared by mixing an equal aliquot of the supernatants from all of the samples.
Sample Type:Breast cancer cells

Treatment:

Treatment ID:TR003279
Treatment Summary:no treatment

Sample Preparation:

Sampleprep ID:SP003277
Sampleprep Summary:For each sample, 1000 μL extract solution (acetonitrile: methanol: water = 2: 2: 1) containing the isotopically-labeled internal standard mixture was added. After 30 seconds of vortex, the samples were homogenized at 35 Hz for 4 min and sonicated for 5 min in an ice-water bath. The homogenization and sonication cycle was repeated 2 times. The samples were sonicated for 5 min in an ice-water bath incubated at -40 ℃ for 1 h and centrifuged at 12000 rpm for 15 min at 4 ℃. 800 μL of supernatant was transferred to a fresh tube and dried in a vacuum concentrator at 37 ℃. Then, the dried samples were reconstituted in 200 μL of 50% acetonitrile by sonication on ice for 10 min. The constitution was then centrifuged at 13000 rpm for 15 min at 4 ℃, and 75 μL of supernatant was transferred to a fresh glass vial for LC/MS analysis. The quality control (QC) sample was prepared by mixing an equal aliquot of the supernatants from all of the samples.

Chromatography:

Chromatography ID:CH003913
Instrument Name:Agilent 1290 Infinity
Column Name:Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um)
Column Temperature:25
Flow Gradient:0-0.5 min, 95%B; 0.5-7.0 min, 95%-65% B; 7.0-8.0 min, 65%-40% B; 8.0-9.0 min, 40% B; 9.0-9.1 min, 40%-95% B; 9.1-12.0 min, 95% B
Flow Rate:2 μl/min
Solvent A:100% water; 25 mmol/L ammonium acetate; 25 mmol/L ammonium hydroxide (pH = 9.75)
Solvent B:100% acetonitrile;25 mmol/L ammonium acetate; 25 mmol/L ammonia hydroxide
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN005173
Analysis Type:MS
Chromatography ID:CH003913
Has Mz:1
Has Rt:1
Rt Units:Seconds
Results File:ST003153_AN005173_Results.txt
Units:Peak area
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