The super elongation complex family of RNA polymerase II elongation factors: Gene target specificity and transcriptional output

Zhuojuan Luo, Chengqi Lin, Erin Guest, Alexander S. Garrett, Nima Mohaghegh, Selene Swanson, Stacy Marshall, Laurence Florens, Michael P. Washburn, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

The elongation stage of transcription is highly regulated in metazoans. We previously purified the AFF1- and AFF4-containing super elongation complex (SEC) as a major regulator of development and cancer pathogenesis. Here, we report the biochemical isolation of SEC-like 2 (SEC-L2) and SEC-like 3 (SEC-L3) containing AFF2 and AFF3 in association with P-TEFb, ENL/MLLT1, and AF9/MLLT3. The SEC family members demonstrate high levels of polymerase II (Pol II) C-terminal domain kinase activity; however, only SEC is required for the proper induction of the HSP70 gene upon stress. Genome-wide mRNA-Seq analyses demonstrated that SEC-L2 and SEC-L3 control the expression of different subsets of genes, while AFF4/SEC plays a more dominant role in rapid transcriptional induction in cells. MYC is one of the direct targets of AFF4/SEC, and SEC recruitment to the MYC gene regulates its expression in different cancer cells, including those in acute myeloid or lymphoid leukemia. These findings suggest that AFF4/SEC could be a potential therapeutic target for the treatment of leukemia or other cancers associated with MYC overexpression.

Original languageEnglish (US)
Pages (from-to)2608-2617
Number of pages10
JournalMolecular and cellular biology
Volume32
Issue number13
DOIs
StatePublished - Jul 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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