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

Perform statistical analysis | Show all samples | Show named metabolites | Download named metabolite data
Download mwTab file (text) | Download mwTab file(JSON)

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

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	TOF	TOF
MS instrument name	Agilent 6230 TOF	Agilent 6230 TOF
Ion Mode	POSITIVE	NEGATIVE
Units	fmol/cell	fmol/cell

MS:

MS ID:	MS003533
Analysis ID:	AN003791
Instrument Name:	Agilent 6230 TOF
Instrument Type:	TOF
MS Type:	ESI
MS Comments:	Electrospray ionization (ESI)-time-of-flight mass spectrometry (TOFMS) was conducted in the positive ion mode and the capillary voltage was set at 4,000V. A flow rate of heated dry nitrogen gas (heater temperature 300 ºC) was maintained at 7 psig. In TOFMS, the fragmentor-, skimmer-, and Oct RFV voltage was set at 75 V, 50 V, and 500V, respectively. Automatic recalibration of each acquired spectrum was performed using reference masses of reference standards. The 13C isotopic ion of a protonated methanol dimer ([2MeOH+H]+, m/z 66.0631) and Hexakis(2,2-difluoroethoxy)phosphazene ([M+H]+, m/z 622.0290) provided the lock mass for exact mass measurements.
Ion Mode:	POSITIVE

MS ID:	MS003534
Analysis ID:	AN003792
Instrument Name:	Agilent 6230 TOF
Instrument Type:	TOF
MS Type:	ESI
MS Comments:	ESI-TOFMS was conducted in the negative ion mode; the capillary voltage was set at 3,500 V. For TOFMS, the fragmentor-, skimmer-, and Oct RFV voltage was set at 100 V, 50 V, and 500 V, respectively. Automatic recalibration of each acquired spectrum was performed using reference masses of reference standards, i.e., 13C isotopic ion of deprotonated acetic acid dimer ([2CH3COOH-H]-, m/z 120.0384), and Hexakis + deprotonated acetic acid (m/z 680.03554) provided the lock mass for exact mass measurements.
Ion Mode:	NEGATIVE