The super elongation complex (SEC) and MLL in development and disease

Edwin Smith, Chengqi Lin, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

228 Scopus citations

Abstract

Transcriptional regulation at the level of elongation is vital for the control of gene expression and metazoan development. The mixed lineage leukemia (MLL) protein and its Drosophila homolog, Trithorax, which exist within COMPASS (complex of proteins associated with Set1)-like complexes, are master regulators of development. They are required for proper homeotic gene expression, in part through methylation of histone H3 on Lys 4. In humans, the MLL gene is involved in a large number of chromosomal translocations that create chimeric proteins, fusing the N terminus of MLL to several proteins that share little sequence similarity. Several frequent translocation partners of MLL were found recently to coexist in a super elongation complex (SEC) that includes known transcription elongation factors such as eleven-nineteen lysine-rich leukemia (ELL) and P-TEFb. Importantly, the SEC is required for HOX gene expression in leukemic cells, suggesting that chromosomal translocations involving MLL could lead to the overexpression of HOX and other genes through the involvement of the SEC. Here, we review the normal developmental roles of MLL and the SEC, and how MLL fusion proteins can mediate leukemogenesis.

Original languageEnglish (US)
Pages (from-to)661-672
Number of pages12
JournalGenes and Development
Volume25
Issue number7
DOIs
StatePublished - Apr 2011

Keywords

  • H3K4 methylation
  • HOX genes
  • Leukemia
  • P-TEFb
  • Transcription elongation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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