Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin
- 22 August 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (36), E636-E645
- https://doi.org/10.1073/pnas.1107107108
Abstract
The Super Elongation Complex (SEC), containing transcription elongation activators/coactivators P-TEFb, ELL2, AFF4/1, ENL, and AF9, is recruited by HIV-1 Tat and mixed lineage leukemia (MLL) proteins to activate the expression of HIV-1 and MLL-target genes, respectively. In the absence of Tat and MLL, however, it is unclear how SEC is targeted to RNA polymerase (Pol) II to stimulate elongation in general. Furthermore, although ENL and AF9 can bind the H3K79 methyltransferase Dot1L, it is unclear whether these bindings are required for SEC-mediated transcription. Here, we show that the homologous ENL and AF9 exist in separate SECs with similar but nonidentical functions. ENL/AF9 contacts the scaffolding protein AFF4 that uses separate domains to recruit different subunits into SEC. ENL/AF9 also exists outside SEC when bound to Dot1L, which is found to inhibit SEC function. The YEATS domain of ENL/AF9 targets SEC to Pol II on chromatin through contacting the human Polymerase-Associated Factor complex (PAFc) complex. This finding explains the YEATS domain’s dispensability for leukemogenesis when ENL/AF9 is translocated to MLL, whose interactions with PAFc and DNA likely substitute for the PAFc/chromatin-targeting function of the YEATS domain.Keywords
This publication has 38 references indexed in Scilit:
- Controlling the Elongation Phase of Transcription with P-TEFbMolecular Cell, 2006
- Dot1a-AF9 Complex Mediates Histone H3 Lys-79 Hypermethylation and Repression of ENaCα in an Aldosterone-sensitive MannerPublished by Elsevier BV ,2006
- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem CellsCell, 2005
- Dynamic Lysine Methylation on Histone H3 Defines the Regulatory Phase of Gene TranscriptionMolecular Cell, 2005
- The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners with chromatinOncogene, 2005
- hDOT1L Links Histone Methylation to LeukemogenesisCell, 2005
- The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryoteGenes & Development, 2004
- The Oncogenic Capacity of HRX-ENL Requires the Transcriptional Transactivation Activity of ENL and the DNA Binding Motifs of HRXMolecular and Cellular Biology, 1998
- ELL2, a new member of an ELL family of RNA polymerase II elongation factorsProceedings of the National Academy of Sciences of the United States of America, 1997
- Paf1p, an RNA Polymerase II-Associated Factor inSaccharomyces cerevisiae, May Have both Positive and Negative Roles in TranscriptionMolecular and Cellular Biology, 1996