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Integrative analysis reveals histone demethylase LSD1 promotes RNA polymerase II pausing
Hani Jieun Kim1,2, Pishun Li3, Taiyun Kim1,2,4
1Computational Systems Biology Group, Children's Medical Research Institute, Westmead, NSW 2145, Australia.
Iscience
|September 20, 2022
Summary
Lysine-specific demethylase 1 (LSD1) promotes RNA polymerase II (RNAPII) pausing in mouse embryonic stem cells. This finding reveals a new role for LSD1 in gene transcription regulation.
Area of Science:
- Molecular Biology
- Developmental Biology
- Epigenetics
Background:
- Lysine-specific demethylase 1 (LSD1) is known to regulate enhancer decommissioning during embryonic stem cell (ESC) differentiation.
- The function of LSD1 at gene promoters is less understood, despite its presence at these regulatory regions.
Purpose of the Study:
- To investigate the role of LSD1 in regulating RNA polymerase II (RNAPII) pausing at gene promoters in ESCs.
- To elucidate the relationship between LSD1, MYC, and RNAPII pausing factors in transcription regulation.
Main Methods:
- Knockdown of LSD1 in ESCs.
- Analysis of RNAPII pausing dynamics.
- Co-localization studies of LSD1 and MYC.
- Protein-protein interaction assays.
- Gene set enrichment analysis.
Main Results:
- LSD1 knockdown preferentially impacts genes with high RNAPII pausing.
- LSD1 co-localizes with MYC at sites enriched for RNAPII pausing factors.
- LSD1 and MYC directly interact, with MYC recruitment dependent on LSD1.
- Genes co-regulated by LSD1 and MYC are enriched for housekeeping functions.
Conclusions:
- LSD1 plays a significant role in promoting RNAPII pausing at gene promoters in ESCs.
- LSD1 interacts with MYC to regulate transcription, influencing housekeeping gene expression.
- This study reveals a pleiotropic function of LSD1 in transcription regulation beyond enhancer modification.
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