Structural highlights
Function
[CTR9_YEAST] The PAF1 complex is a multifunctional complex. Involved in transcription initiation via genetic interactions with TATA-binding proteins. Involved in elongation. It regulates 3'-end formation of snR47 by modulating the recruitment or stable association of NRD1 and NAB3 with RNA polymerase II. Also has a role in transcription-coupled histone modification. Required for activation of RAD6 ubiquitin conjugate and the BRE1 ubiquitin ligase which ubiquitinate 'Lys-126' histone H2B. Activates the SET1 histone methyltransferase complex for methylation of 'Lys-4' of histone H3 and for methylation of 'Lys-73' of histone H3 by DOT1 and 'Lys-36' of histone H3 by SET2. In complex with PAF1, required for normal CLN1 and CLN2 G1 cyclin expression in late G1. Also has a role in chromosome segregation where it appears to be involved in microtubule placement.[1] [2] [3] [4]
Publication Abstract from PubMed
The evolutionarily conserved multifunctional polymerase-associated factor 1 (Paf1) complex (Paf1C), which is composed of at least five subunits (Paf1, Leo1, Ctr9, Cdc73, and Rtf1), plays vital roles in gene regulation and has connections to development and human diseases. Here, we report two structures of each of the human and yeast Ctr9/Paf1 subcomplexes, which assemble into heterodimers with very similar conformations, revealing an interface between the tetratricopeptide repeat module in Ctr9 and Paf1. The structure of the Ctr9/Paf1 subcomplex may provide mechanistic explanations for disease-associated mutations in human PAF1 and CTR9. Our study reveals that the formation of the Ctr9/Paf1 heterodimer is required for the assembly of yeast Paf1C, and is essential for yeast viability. In addition, disruption of the interaction between Paf1 and Ctr9 greatly affects the level of histone H3 methylation in vivo. Collectively, our results shed light on Paf1C assembly and functional regulation.
Paf1 and Ctr9 subcomplex formation is essential for Paf1 complex assembly and functional regulation.,Xie Y, Zheng M, Chu X, Chen Y, Xu H, Wang J, Zhou H, Long J Nat Commun. 2018 Sep 18;9(1):3795. doi: 10.1038/s41467-018-06237-7. PMID:30228257[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Koch C, Wollmann P, Dahl M, Lottspeich F. A role for Ctr9p and Paf1p in the regulation G1 cyclin expression in yeast. Nucleic Acids Res. 1999 May 15;27(10):2126-34. PMID:10219085
- ↑ Porter SE, Penheiter KL, Jaehning JA. Separation of the Saccharomyces cerevisiae Paf1 complex from RNA polymerase II results in changes in its subnuclear localization. Eukaryot Cell. 2005 Jan;4(1):209-20. PMID:15643076 doi:http://dx.doi.org/10.1128/EC.4.1.209-220.2005
- ↑ Sheldon KE, Mauger DM, Arndt KM. A Requirement for the Saccharomyces cerevisiae Paf1 complex in snoRNA 3' end formation. Mol Cell. 2005 Oct 28;20(2):225-36. PMID:16246725 doi:S1097-2765(05)01568-6
- ↑ Foreman PK, Davis RW. CDP1, a novel Saccharomyces cerevisiae gene required for proper nuclear division and chromosome segregation. Genetics. 1996 Dec;144(4):1387-97. PMID:8978028
- ↑ Xie Y, Zheng M, Chu X, Chen Y, Xu H, Wang J, Zhou H, Long J. Paf1 and Ctr9 subcomplex formation is essential for Paf1 complex assembly and functional regulation. Nat Commun. 2018 Sep 18;9(1):3795. doi: 10.1038/s41467-018-06237-7. PMID:30228257 doi:http://dx.doi.org/10.1038/s41467-018-06237-7
