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A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
Published on: December 4, 2018
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Calcineurin/NFATc1 pathway represses cellular cytotoxicity by modulating histone H3 expression
Yuki Sato1, Makoto Habara1, Shunsuke Hanaki1
1Department of Veterinary Biochemistry, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8511, Japan.
Scientific Reports
|June 26, 2024
Summary
Excess histones cause genomic instability. The transcription factor NFATc1 (nuclear factor of activated T cells 1) represses histone gene expression, preventing harmful histone accumulation and maintaining cell survival.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Excess histones lead to mitotic chromosome loss and genomic instability, threatening cell survival.
- Histone degradation in yeast involves the proteasome and Rad53, but transcriptional regulation remains unclear.
Purpose of the Study:
- To investigate the transcriptional regulation of histone genes.
- To identify factors controlling histone expression and their role in preventing genomic instability.
Main Methods:
- Treatment with calcineurin inhibitors.
- Analysis of transcription factor NFATc1 binding to histone gene promoters.
- Assessment of histone gene expression in response to intracellular calcium levels.
- Cell proliferation assays upon histone H3 overexpression.
Main Results:
- Calcineurin inhibitor treatment elevated histone protein levels.
- NFATc1 was identified as a repressor of histone transcription, acting downstream of calcineurin.
- NFATc1 binds to promoters of multiple histone genes.
- Histone transcription is downregulated by intracellular calcium levels.
- Overexpression of histone H3 significantly impaired cell proliferation.
Conclusions:
- NFATc1 plays a crucial role in preventing detrimental histone accumulation.
- NFATc1 maintains genomic stability by repressing histone gene expression transcriptionally.
- Intracellular calcium levels modulate histone transcription via NFATc1.
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