The PAF Complex Synergizes with MLL Fusion Proteins at HOX Loci to Promote Leukemogenesis

Andrew G. Muntean, Jiaying Tan, Kajal Sitwala, Yongsheng Huang, Joel Bronstein, James A. Connelly, Venkatesha Basrur, Kojo S.J. Elenitoba-Johnson, Jay L. Hess

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

MLL is involved in chromosomal rearrangements that generate fusion proteins with deregulated transcriptional activity. The mechanisms of MLL fusion protein-mediated transcriptional activation are poorly understood. Here we show MLL interacts directly with the polymerase associated factor complex (PAFc) through sequences flanking the CxxC domain. PAFc interacts with RNA polymerase II and stimulates posttranslational histone modifications. PAFc augments MLL and MLL-AF9 mediated transcriptional activation of Hoxa9. Conversely, knockdown of PAFc disrupts MLL fusion protein-mediated transcriptional activation and MLL recruitment to target loci. PAFc gene expression is downregulated during hematopoiesis and likely serves to regulate MLL function. Deletions of MLL that abolish interactions with PAFc also eliminate MLL-AF9 mediated immortalization indicating an essential function for this interaction in leukemogenesis.

Original languageEnglish (US)
Pages (from-to)609-621
Number of pages13
JournalCancer Cell
Volume17
Issue number6
DOIs
StatePublished - Jun 15 2010

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Keywords

  • CELLCYCLE
  • DNA
  • HUMDISEASE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Muntean, A. G., Tan, J., Sitwala, K., Huang, Y., Bronstein, J., Connelly, J. A., Basrur, V., Elenitoba-Johnson, K. S. J., & Hess, J. L. (2010). The PAF Complex Synergizes with MLL Fusion Proteins at HOX Loci to Promote Leukemogenesis. Cancer Cell, 17(6), 609-621. https://doi.org/10.1016/j.ccr.2010.04.012