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 |
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Treatment:
| Treatment ID: | TR002422 |
| Treatment Summary: | Cells were treated with dTAG-13 for 24 h or 48 h. |
| Treatment Compound: | dTAG-13 |
