Summary of project PR001489
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
| Project ID: | PR001489 |
| Project DOI: | doi: 10.21228/M88414 |
| Project Title: | SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia |
| Project 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 |
Summary of all studies in project PR001489
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002323 | SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia | Homo sapiens | Chiba University | MS | 2022-11-18 | 1 | 12 | Not available |
