Use this URL to cite or link to this record in EThOS:
Title: The super elongation complex (SEC) in development and disease
Author: Lin , Chengqi
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2012
Availability of Full Text:
Access from EThOS:
Chromosomal translocations involving the mixed lineage leukemia (MLL) gene are associated with infant acute leukemia. There are a large number of translocation partners of MLL that share very little sequence similarities, yet their translocations into MLL result in the pathogenesis of leukemia. To define the molecular reason why these translocations result in leukemogenesis, I purified several of the commonly occurring MLL chimeras and identified a novel Super Elongation Complex (SEC) associated with all chimeras purified. SEC consists of the RNA Pol II elongation factors ELLl -3, P-TEFb, and several frequent MLL-translocation partners. SEC is one of the most active P-TEFb complexes and is required for the proper expression ofMLL chimera target genes and the oncogene, MYe, 1 suggesting that the regulation of transcription elongation checkpoint control (TEeC) by SEC could play essential roles in leukemia. Paused Pol II has been proposed to be associated with loci that respond rapidly to environmental stimuli. My studies in mouse ES cells demonstrated that SEC is required for rapid transcriptional activation of genes, many of which contain paused Pol II. However, SEC is also required for the activation of the Cyp26aJ gene, which does not contain detectable Pol II, yet responds much more rapidly to retinoic acid than those paused genes, suggesting that paused Pol II is not a prerequisite for rapid gene activation. Furthermore, EIl3, a member of the ELL fami ly of proteins, predominately occupies poised, active, and inactive enhancers of many developmental genes in ES cells. E113's association with enhancers is required for setting up proper Pol II occupancy at the promoter-proximal regions of neighboring genes, providing a yet to be discovered mechanism for the transition from El13's presence at poised enhancers in ES cells to E112 's role in the release of paused Pol II during gene activation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available