Summary of Study ST002323

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 PR001489. The data can be accessed directly via it's Project DOI: 10.21228/M88414 This work is supported by NIH grant, U2C- DK119886.

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Study ID	ST002323
Study Title	SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia
Study Summary	Histone methyltransferase SETD1A is critical for acute myeloid leukemia (AML) cell survival, but the molecular mechanism driving SETD1A gene regulation remains elusive. To delineate the role of SETD1A, we utilize a protein degrader technology to induce rapid SETD1A degradation in AML cell lines. SETD1A degradation results in immediate downregulation of transcripts associated with DNA repair and heme biosynthesis pathways. CRISPR-based functional analyses and metabolomics reveal an essential role of SETD1A to maintain mitochondrial respiration in AML cells. These SETD1A targets are enriched in head-to-head (H2H) genes. SETD1A degradation disrupts a non-enzymatic SETD1A domain-dependent cyclin K function, increases the Ser5P RNA polymerase II (RNAP2) at TSS, and induces the promoter-proximal pausing of RNAP2 in a strand-specific manner. This study reveals a non-enzymatic role for SETD1A in transcriptional pause release and provides insight into the mechanism of RNAP2 pausing and its function in cancer.
Institute	Chiba University
Last Name	Hoshii
First Name	Takayuki
Address	1-8-1 Inohana Chuo-ku, Chiba, Chiba, 2608670, Japan
Email	hoshiit@chiba-u.jp
Phone	81432262039
Submit Date	2022-10-12
Analysis Type Detail	LC-MS
Release Date	2022-11-18
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP002416
Sampleprep Summary:	For anionic metabolite analysis, the original Agilent stainless ESI needle was replaced with the Agilent G7100-60041 platinum ESI needle. System control and data acquisition were performed by Agilent MassHunter Workstation, and data analysis was done by Keio MasterHands software. For cationic metabolite analysis, separations were carried out in a fused silica capillary (50 µm i.d. x 100 cm total length) filled with 1 M formic acid as the electrolyte. Approximately 5 nL of sample solution were injected at 50 mbar for 5 sec and 30 kV of voltage was applied. The capillary temperature was maintained at 20 ºC and the sample tray was cooled below 5 ºC. Methanol-water (50 % v/v) containing 0.01 µM Hexakis(2,2-difluoroethoxy)phosphazene was delivered as the sheath liquid at 10 µL/min.

Sampleprep ID:

SP002416

Sampleprep Summary:

For anionic metabolite analysis, the original Agilent stainless ESI needle was replaced with the Agilent G7100-60041 platinum ESI needle. System control and data acquisition were performed by Agilent MassHunter Workstation, and data analysis was done by Keio MasterHands software. For cationic metabolite analysis, separations were carried out in a fused silica capillary (50 µm i.d. x 100 cm total length) filled with 1 M formic acid as the electrolyte. Approximately 5 nL of sample solution were injected at 50 mbar for 5 sec and 30 kV of voltage was applied. The capillary temperature was maintained at 20 ºC and the sample tray was cooled below 5 ºC. Methanol-water (50 % v/v) containing 0.01 µM Hexakis(2,2-difluoroethoxy)phosphazene was delivered as the sheath liquid at 10 µL/min.