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Updated: Mar 25, 2026
12:36
In vitro tRNA Methylation Assay with the Entamoeba histolytica DNA and tRNA Methyltransferase Dnmt2 Ehmeth Enzyme
Published on: October 19, 2010
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SETD2 methyltransferase activity promotes correct transcription initiation and termination
Magda Kopczyńska1,2, Chihiro Nakayama3,4, Agata Stępień1,2
1Center for Advanced Technologies, Adam Mickiewicz University, Uniwersytetu Poznanskiego 10, 61-614, Poznan, Poland.
EMBO Reports
|March 24, 2026
Summary
The SETD2 enzyme plays a dual role in gene regulation. Loss of SETD2 function impacts transcription initiation and termination, particularly for specific gene classes, affecting cancer development.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Biology
Background:
- SETD2 is a crucial methyltransferase for histone H3 lysine 36 trimethylation (H3K36me3).
- Loss of SETD2 activity is implicated in cancers like renal cell carcinoma.
- SETD2 mutations are linked to transcription termination defects, requiring deeper investigation.
Purpose of the Study:
- To investigate the precise functions of SETD2 in transcription initiation and termination.
- To explore the dichotomy of SETD2's role in different gene classes.
- To understand the consequences of SETD2 loss on gene expression and cancer.
Main Methods:
- Utilized nascent transcriptomics in SETD2 knockout and patient-derived cells.
- Analyzed transcription initiation, termination, and 3' pre-mRNA processing.
- Investigated alternative polyadenylation events.
Main Results:
- Identified two classes of genes (Class I and Class II) with distinct SETD2 dependencies.
- Class I genes require SETD2 for initiation but terminate normally.
- Class II genes show robust initiation without SETD2 but exhibit widespread transcriptional readthrough, increased cryptic initiation, and impaired 3' end processing.
Conclusions:
- SETD2's methyltransferase activity indirectly promotes proper transcription initiation and efficient 3' end processing.
- SETD2 loss leads to defective termination and increased cryptic transcription initiation, particularly affecting Class II genes.
- Alternative polyadenylation is cell-type specific and not directly linked to readthrough upon SETD2 loss.
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