Summary of Study ST002323

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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 IDST002323
Study TitleSETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia
Study SummaryHistone 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.
Chiba University
Last NameHoshii
First NameTakayuki
Address1-8-1 Inohana Chuo-ku, Chiba, Chiba, 2608670, Japan
Submit Date2022-10-12
Analysis Type DetailLC-MS
Release Date2022-11-18
Release Version1
Takayuki Hoshii Takayuki Hoshii application/zip

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Subject ID:SU002410
Subject Type:Cultured cells
Subject Species:Homo sapiens
Taxonomy ID:9606
Cell Strain Details:MOLM-13 cells expressing FKBPF36V-tagged SETD1A