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Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes
1Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
The EMBO Journal
|June 5, 1999
Summary
The lymphoid factors Ikaros and Aiolos act as transcriptional repressors by interacting with histone deacetylase complexes. This mechanism regulates gene expression during lymphocyte development.
Area of Science:
- Molecular Biology
- Gene Regulation
- Immunology
Background:
- Lymphocyte development relies on precise gene expression control.
- The lymphoid factors Ikaros and Aiolos are crucial for determining lymphoid cell lineages.
- Transcriptional regulation involves complex interactions between proteins and DNA.
Purpose of the Study:
- To investigate the mechanism by which Ikaros and Aiolos function as transcriptional repressors.
- To determine the role of histone acetylation and deacetylation in Ikaros-mediated repression.
- To identify co-repressor proteins interacting with Ikaros and Aiolos.
Main Methods:
- Analysis of Ikaros and Aiolos protein domains involved in repression.
- Assessment of histone acetylation levels at target promoters.
- In vivo and in vitro interaction studies with co-repressor complexes.
- Treatment with histone deacetylase inhibitors.
Main Results:
- Ikaros and Aiolos function as potent transcriptional repressors through specific domains.
- Repression is context-dependent on promoter and cell type.
- Ikaros-mediated repression correlates with reduced histone acetylation.
- Ikaros proteins interact with mSin3 and Mi-2-HDAC co-repressor complexes.
Conclusions:
- Ikaros family members recruit histone deacetylase complexes to modulate gene expression.
- This recruitment is critical for regulating gene expression during lymphocyte development.
- The findings elucidate a key mechanism in lymphoid lineage determination.