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Purification and characterization of the human elongator complex
Nicola A Hawkes1, Gabriel Otero, G Sebastiaan Winkler
1Mechanisms of Gene Transcription Laboratory, Imperial Cancer Research Fund Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire, EN6 3LD, United Kingdom.
The Journal of Biological Chemistry
|November 21, 2001
Summary
The human Elongator complex, involved in transcription, exists in two forms. Mutations in a subunit (IKAP) linked to familial dysautonomia suggest a potential transcription disorder.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- The Elongator complex is crucial for gene transcription.
- Its role in human cells and associated diseases is not fully understood.
Purpose of the Study:
- To characterize the human Elongator complex and its functions.
- To investigate the link between Elongator complex dysfunction and familial dysautonomia.
Main Methods:
- Purification of the human Elongator complex from HeLa cell extracts.
- Biochemical assays to determine histone acetyltransferase activity.
- Identification of Elongator complex subunits and interactions with RNA polymerase II.
Main Results:
- The human Elongator complex was purified and found to exist in two forms: holo-Elongator (six subunits, with histone acetyltransferase activity) and a three-subunit core form (lacking activity).
- Elongator is a component of early transcription elongation complexes and interacts with RNA polymerase II.
- Human homologues of yeast Elongator subunits, including StIP1 and IKAP, were identified.
Conclusions:
- The human Elongator complex possesses distinct functional forms.
- Mutations in IKAP, an Elongator subunit, causing familial dysautonomia, suggest this disorder may stem from compromised Elongator function, potentially classifying it as a transcription disorder.