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BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs
Rebecca Mathew1, Michael P Seiler, Seth T Scanlon
1Committee on Immunology, Department of Pathology, The Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637, USA.
Nature
|October 23, 2012
Summary
Promyelocytic leukaemia zinc finger (PLZF) and BCL6 transcription factors recruit cullin 3 (CUL3) to modify chromatin. This interaction is crucial for T- and B-cell differentiation and may play a role in certain cancers.
Area of Science:
- Immunology
- Molecular Biology
- Epigenetics
Background:
- Transcription factors direct T- and B-cell effector programs via epigenetic remodeling.
- BTB-zinc finger (BTB-ZF) proteins are key regulators in these processes.
Purpose of the Study:
- To investigate the interaction between PLZF and CUL3.
- To elucidate the role of CUL3 in BTB-ZF-mediated cellular differentiation.
Main Methods:
- Co-immunoprecipitation to assess protein associations.
- Nuclear localization studies of PLZF and CUL3.
- Ubiquitination assays.
- Conditional gene deletion in mice to study lineage development.
Main Results:
- PLZF forms a complex with CUL3 in the nucleus.
- PLZF facilitates CUL3-mediated ubiquitination of chromatin-modifying complex components.
- CUL3 is essential for the development of PLZF- and BCL6-dependent cell lineages.
- CUL3 also associates with BCL6, another BTB-ZF transcription factor.
Conclusions:
- Lineage-specific BTB-ZF transcription factors recruit CUL3 to modulate their associated chromatin-modifying complexes.
- This recruitment alters ubiquitination patterns, essential for T- and B-cell differentiation.
- The PLZF-CUL3 and BCL6-CUL3 interactions may contribute to the oncogenic roles of these factors in leukemia and lymphoma.
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