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Updated: May 7, 2026
14:40
Expression Analysis of Mammalian Linker-histone Subtypes
Published on: March 19, 2012
macroH2A1 histone variant represses rDNA transcription
Rong Cong1, Sadhan Das, Julien Douet
1Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS USR 3010, Laboratoire Joliot-Curie, 69364 Lyon, France, The Institute of Predictive and Personalized Medicine of Cancer (IMPPC), 08916 Badalona, Barcelona, Spain and The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
Nucleic Acids Research
|September 28, 2013
Summary
The histone variant macroH2A1 regulates ribosomal DNA (rDNA) transcription. Inhibiting macroH2A1 increases pre-ribosomal RNA (pre-rRNA) levels, revealing its role in controlling cell growth.
Area of Science:
- Molecular Biology
- Epigenetics
- Cell Biology
Background:
- Ribosomal DNA (rDNA) transcription is crucial for cell growth regulation.
- Epigenetic modifications like DNA methylation and histone modifications control rDNA transcription.
- The role of histone variants in rDNA transcription remains largely unexplored.
Purpose of the Study:
- To investigate the role of the histone variant macroH2A1 in regulating ribosomal DNA transcription.
- To determine how macroH2A1 affects pre-ribosomal RNA (pre-rRNA) synthesis and RNA polymerase I loading.
Main Methods:
- Inhibition of macroH2A1 expression in human cell lines (HeLa, HepG2) and mouse ES cells.
- Measurement of pre-rRNA levels and RNA polymerase I/UBF loading on rDNA.
- Analysis of macroH2A1 recruitment to rDNA upon transcription inhibition (actinomycin D, nucleolin knockdown).
Main Results:
- macroH2A1 is localized to the promoter of methylated rDNA genes.
- Inhibition of macroH2A1 led to a 5-fold increase in pre-rRNA levels.
- Increased pre-rRNA correlated with enhanced RNA polymerase I and UBF loading on rDNA.
- Transcription inhibition induced macroH2A1 recruitment to rDNA and nucleolar relocalization.
- macroH2A1 inactivation alleviated nucleolin depletion-induced rDNA transcription inhibition.
Conclusions:
- macroH2A1 is a novel factor involved in the regulation of ribosomal DNA transcription.
- macroH2A1 acts as a repressor of rDNA transcription.
- macroH2A1 plays a significant role in controlling cell growth through rDNA transcription regulation.
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