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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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 |
hoshiit@chiba-u.jp | |
Phone | 81432262039 |
Submit Date | 2022-10-12 |
Analysis Type Detail | LC-MS |
Release Date | 2022-11-18 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN003791 | AN003792 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | CE | CE |
Chromatography system | Agilent 7100 CE | Agilent 7100 CE |
Column | COSMO(+) (chemically coated with cationic polymer) capillary (50um x 105cm total length) (Nacalai Tesque,Kyoto,Japan) | COSMO(+) (chemically coated with cationic polymer) capillary (50um x 105 cm total length) (Nacalai Tesque,Kyoto,Japan) |
MS Type | ESI | ESI |
MS instrument type | QTOF | QTOF |
MS instrument name | Agilent 6230 TOF | Agilent 6230 TOF |
Ion Mode | POSITIVE | NEGATIVE |
Units | fmol/cell | fmol/cell |
Chromatography:
Chromatography ID: | CH002804 |
Chromatography Summary: | 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. |
Instrument Name: | Agilent 7100 CE |
Column Name: | COSMO(+) (chemically coated with cationic polymer) capillary (50um x 105cm total length) (Nacalai Tesque,Kyoto,Japan) |
Chromatography Type: | CE |
Chromatography ID: | CH002805 |
Chromatography Summary: | For anionic metabolite analysis, a commercially available COSMO(+) (chemically coated with cationic polymer) capillary (50 µm i.d. x 105 cm total length) (Nacalai Tesque, Kyoto, Japan) was used with a 50 mM ammonium acetate solution (pH 8.5) as the electrolyte. Sample solution (30 nL) was injected at 50 mbar for 30 sec and -30 kV of voltage was applied. Ammonium acetate (5 mM) in 50 % methanol-water (v/v) containing 0.01 µM Hexakis(2,2-difluoroethoxy)phosphazene was delivered as the sheath liquid at 10 µl/min. |
Instrument Name: | Agilent 7100 CE |
Column Name: | COSMO(+) (chemically coated with cationic polymer) capillary (50um x 105 cm total length) (Nacalai Tesque,Kyoto,Japan) |
Chromatography Type: | CE |