Chengqi LIN 
                       
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  Chengqi LIN  
  Lab Location: #5-07

email:
cqlin@imcb.a-star.edu.sg
tel:65869532
 
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  Key Publications  
 

The RNA Pol II elongation factor Ell3 marks enhancers in ES cells and primes future gene activation. Lin C, Garrus AS, Luo Z, Guo F, Shilatifard A.
Cell. 2013 Jan 17;152(1-2):144-56.

The super elongation complex (SEC) family in transcriptional control.
Luo Z, Lin C, Shilatifard A.
Nat Rev Mol Cell Biol. 2012 Aug 16;13(9):543-7.

The super elongation complex family of RNA polymerase II elongation factors: gene target specificity and transcriptional output.
Luo Z, Lin C, Guest E, Garrett AS, Mohaghegh N, Swanson S, Marshall S, Florens L, Washburn MP, Shilatifard A.
Mol Cell Biol. 2012 Jul;32(13):2608-17.

Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC). Lin C, Garrett AS, De Kumar B, Smith ER, Gogol M, Seidel C, Krumlauf R, Shilatifard A.
Genes Dev. 2011 Jul 15;25(14):1486-98.

Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis.
Mohan M, Lin C, Guest E, Shilatifard A.
Nat Rev Cancer. 2010 Oct;10(10):721-8.

AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia.
Lin C, Smith ER, Takahashi H, Lai KC, Martin-Brown S, Florens L, Washburn MP, Conaway JW, Conaway RC, Shilatifard A.
Mol Cell. 2010 Feb 12;37(3):429-37.

Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II.
Wang P, Lin C, Smith ER, Guo H, Sanderson BW, Wu M, Gogol M, Alexander T, Seidel C, iedemann LM, Ge K, Krumlauf R, Shilatifard A.
Mol Cell Biol. 2009 Nov;29(22):6074-85

 

 

 
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  Chengqi LIN


Chengqi Lin obtained his Ph.D. degree in molecular and cell biology at the Stowers Institute for Medical Research in 2013. His doctoral work was performed at Ali Shilatifard laboratory, where he identified the Super Elongation Complex (SEC) and characterized its essential roles in development and leukemogenesis. This work is recommended by the Faculty of 1000, which identifies the most significant articles in biomedical research publications. He also found that the transcriptional elongation factor Ell3 could serve as a unique epigenetic marker by bookmarking the inactive enhancers of genes for future activation during early development or as early as in germ cells. In 2013, he was awarded an IMCB Junior Investigator (IJI) position to conduct independent research at IMCB.

     
  Transcriptional Control in Development and Disease
 


The pathogenesis of leukemia is a multi-step process initiating from chromosomal translocation or genetic mutations in hematopoietic precursors, which provide proliferation advantage to the precursor cells, but impair their ability to undergo terminal differentiation and apoptosis. Translocations involving the Mixed Lineage Leukaemia (MLL) gene are found frequently in both de novo and secondary leukaemias, representing 80~90% of infant acute lymphoid leukemia (ALL) and ~40% of infant acute myeloid leukemia (AML). Leukemias associated with MLL gene rearrangements are difficult to treat and have poor clinical outcome with overall survival rate of less than 40%. There are a large number of translocation partners of MLL that share very little sequence similarities, yet their translocations into MLL result in leukemogenesis.
We have identified the Super Elongation Complex (SEC), which consists of the RNA Pol II elongation factors ELL1-3, positive transcription elongation factor P-TEFb, and several frequent MLL-translocation partners. The requirement of SEC for the aberrant expression of the MLL chimera target genes and also the oncogene MYC, indicating that the regulation of transcription elongation checkpoint control by SEC could play essential roles in leukemias. In addition to its critical role in leukemogenesis, SEC also functions in the regulated release of paused Pol II into productive elongation and transcriptional activation during stem cell differentiation. Besides SEC, the other two P-TEFb-containing SEC-like complexes (SEC-L2 and SEC-L3) have also been characterized.

In embryonic stem cells, the SEC subunit Ell3 predominately occupies poised, active, and inactive enhancers of many developmentally regulated genes.  Ell3’s association with poised and inactive enhancers is required for setting up proper Pol II occupancy at the promoter-proximal regions of neighboring genes, and their future transcriptional activation by SEC during stem cell differentiation. These observations underlie a mechanism for the transition from Ell3’s presence at poised enhancers in ES cells to SEC’s role in the release of paused Pol II for rapid and synchronous transcriptional activation during development.



Figure Legend:
Super Elongation Complex (SEC) consists of the RNA Pol II elongation factors ELL1-3, positive transcription elongation factor P-TEFb, and several frequent MLL-translocation partners. AFF family proteins are the central components of the complexes, requiring for the assembly of the complex. Each of the AFF family proteins correlates with different kinds of diseases in humans.