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The Roles of the Paf1 Complex and Associated Histone Modifications in Regulating Gene Expression

By Elia M. Crisucci and Karen M. Arndt


The conserved Paf1 complex (Paf1C) carries out multiple functions during transcription by RNA polymerase (pol) II, and these functions are required for the proper expression of numerous genes in yeast and metazoans. In the elongation stage of the transcription cycle, the Paf1C associates with RNA pol II, interacts with other transcription elongation factors, and facilitates modifications to the chromatin template. At the end of elongation, the Paf1C plays an important role in the termination of RNA pol II transcripts and the recruitment of proteins required for proper RNA 3′ end formation. Significantly, defects in the Paf1C are associated with several human diseases. In this paper, we summarize current knowledge on the roles of the Paf1C in RNA pol II transcription

Topics: Review Article
Publisher: SAGE-Hindawi Access to Research
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Provided by: PubMed Central

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  1. (2008). A .B .F l e m i n g ,C .F .K a o ,C .H i l l y e r ,M .P i k a a r t ,a n dM
  2. (2011). A common telomeric gene silencing assay is affected by nucleotide metabolism,”
  3. (2003). A conserved RING finger protein required for histone H2B monoubiquitination and cell size control,”
  4. (2005). A high-resolution map of active promoters in the human genome,”
  5. (1993). A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SW12-like helicase domain,”
  6. (1996). A novel collection of accessory factors associated with yeast
  7. (2005). A posttranscriptional role for the yeast Paf1-RNA polymerase II complex is revealed by identification of primary targets,”
  8. (2005). A requirement for the Saccharomyces cerevisiae
  9. (1999). A role for Ctr9p and Paf1p in the regulation G1 cyclin expression in yeast,”
  10. (2008). A TFTC/STAGA module mediateshistoneH2AandH2Bdeubiquitination,coactivates nuclear receptors, and counteracts heterochromatin silencing,”
  11. (2002). Active genes are tri-methylated at
  12. (2011). Akimov et al., “Systemwide temporal characterization of the proteome and phosphoproteomeofhumanembryonicstemcelldifferentiation,”
  13. (2006). Analysis of nucleosome repositioning by yeast
  14. (2003). Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection ofGenetics
  15. (2005). BUR kinase selectivelyregulatesH3K4trimethylationandH2Bubiquitylation through recruitment of the PAF elongation complex,”
  16. (2003). Bur1 kinase is required for efficient transcription elongation by RNA polymerase
  17. (2004). c h w a r t z ,J .W e r n e r ,J .R .S u a r e z ,a n dJ
  18. (1997). Cdc73p and Paf1p are found in a novel RNA polymerase II-containing complex distinct from the Srbp-containing holoenzyme,”
  19. (1999). CHD1 interacts with SSRP1 and depends on both its chromodomain and its ATPase/helicase-like domain for proper association with chromatin,”
  20. (1996). CHD1 is concentrated in interbands and puffed regions of Drosophila polytenechromosomes,”ProceedingsoftheNationalAcademy
  21. (2003). Chromatin remodeling protein Chd1 interacts with transcription elongation factors and localizes to transcribed genes,”
  22. (1974). Chromatin structure: a repeating unit of histones and
  23. (2007). Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin,”
  24. (2002). COMPASS, a histone H3 (lysine 4) methyltransferase required for telomeric silencing of gene expression,”
  25. (1997). Crystal structure of the nucleosome core particle at 2.8
  26. (2006). De FACTo nucleosome dynamics,”
  27. (2002). Defects in SPT16 or POB3 (yFACT) in Saccharomyces cerevisiae cause dependence on the Hir/Hpc pathway: polymerase passage may degrade chromatin structure,”
  28. (2008). Derailing the locomotive: transcription termination,”
  29. (1994). Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization,”
  30. (2004). Deubiquitination of Histone H2B by a Yeast Acetyltransferase Complex Regulates Transcription,”
  31. (2000). Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription,”
  32. (2008). DirectinteractionsbetweenthePaf1complexandacleavage and polyadenylation factor are revealed by dissociation of
  33. (2005). Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo,”
  34. (2002). Dot1p modulates silencing in yeast by methylation of the nucleosome core,”
  35. (2005). Double chromodomains cooperate to recognize the methylated histone H3 tail,”
  36. Dual roles for Spt5 in pre-mRNA processing and transcription elongation revealed by identification of Spt5-associated proteins,”
  37. (2008). E.Shema,I.Tirosh,Y.Aylonetal.,“ThehistoneH2B-specific ubiquitin ligase RNF20/hBREl acts as a putative tumor suppressor through selective regulation of gene expression,”
  38. (2004). Evidence for nucleosome depletion at active regulatory regions genome-wide,”
  39. (2002). Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo,”
  40. (1998). FACT, a factor that facilitates transcript elongation through nucleosomes,” Cell,v o l .9 2 ,n o .1 ,p p .
  41. (2007). Functions of SiteSpecific histone acetylation and deacetylation,”
  42. (2001). Genetic interactions of
  43. (2006). Genome-wide distribution of yeast RNA polymerase II and its control by
  44. (2005). Genomewide map of nucleosome acetylation and methylation in yeast,”
  45. (2009). h o u ,W .H .W .K u o ,J .F i l l i n g h a m ,a n dJ .F .G r e e n b l a t t , “Control of transcriptional elongation and cotranscriptional
  46. (2002). H.H.Ng,Q.Feng,H.Wangetal.,“Lysinemethylationwithin the globular domain of histone H3 by Dot1 is important for telomeric silencing and
  47. H.H.Ng,R.M.Xu,Y.Zhang,andK.Struhl,“Ubiquitination of histone H2B by Rad6 is required for efficient
  48. (2007). hCTR9, a component ofPaf1complex, participates inthetranscription of interleukin 6-responsive genes through regulation of STAT3-DNA interactions,”
  49. (2009). Histone chaperone Spt16 promotes redeposition of the original H3-H4 histones evicted by elongating RNA polymerase,”
  50. (2011). Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction,”
  51. (2009). Histone H3 lysine 36 dimethylation (H3K36me2) is sufficient to recruit the Rpd3s Histone deacetylase complex and to repress spurious transcription,”
  52. (2005). Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains,”
  53. (2005). i a o ,C .F .K a o ,N .J .K r o g a ne ta l . ,“ H i s t o n eH 2 B ubiquitylation is associated withelongating RNA polymerase II,”MolecularandCellularBiology,vol.25,no.2,pp.637–651,
  54. (1997). Identification of RTF1, a novel gene important for TATA site selection by TATA box-binding protein
  55. inhibits TFIIS-facilitated transcriptional elongation to suppress prooncogenic gene expression,” Molecular Cell,v o l .4 2 ,n o .4 ,p p .
  56. (2005). Interaction between transcription elongation factors and mRNA 3-end formation at the Saccharomyces cerevisiae GAL10-GAL7 locus,”
  57. (1988). Isolation and characterization of two genes encoding yeast mating pheromone signaling elements:
  58. (2004). K a o ,C .H i l l y e r ,T .T s u k u d a ,K .H e n r
  59. (2003). K r o g a n ,M .K i m ,A .T o n ge ta l . ,“ M e t h y l a t i o no f histone H3 by
  60. (2003). K.W.Henry,A.Wyce,W.S.Loetal.,“Transcriptionalactivation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated
  61. (2011). K.Y.KimandD.E.Levin,“Mpk1MAPKassociationwiththe paf1 complex blocks sen1-mediated premature transcription termination,”
  62. (2003). Kahnoski et al., “HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours,”
  63. (2003). Kotovic et al., “The histone 3 lysine methyltransferase, SET2, is involved in transcriptional elongation,”
  64. (2006). L.David,W.Huber,M.Granovskaiaetal.,“Ahigh-resolution map of transcription in the yeast genome,”
  65. (2011). Mass spectrometric studies on epigenetic interaction networks in cell differentiation,”
  66. (2004). Molecular evidence indicating that the yeast PAF complex is required for transcription elongation,”
  67. (2008). Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells,”
  68. (2005). Monoubiquitination of human histone H2B: the factors involved and their roles
  69. (2011). Nascent transcript sequencing visualizes transcription at nucleotide resolution,”
  70. (2010). Nucleosome depletion at yeast terminators is not intrinsic and can occur by a transcriptional mechanism linked to 3-end formation,”
  71. (1953). o u s ,A .G .R o n d ´ o n ,M .G a r c ´
  72. (2007). Overlapping pathways dictate termination of RNA polymerase
  73. (2007). Paf1 complex homologues are required for Notchregulated transcription during somite segmentation,”
  74. (1996). Paf1p, an RNA polymerase II-associated factor in Saccharomyces cerevisiae, may have both positive and negative roles in transcription,”
  75. (2010). PAFc, a key player in MLL-rearranged leukemogenesis,”
  76. (2006). Parafi-bromin/Hyrax Activates Wnt/Wg Target Gene Transcription by Direct Association with β-catenin/Armadillo,”
  77. (2006). Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours,”
  78. (2008). Pfeiffe r ,A .W .T h o r n e ,a n dS .B .M c M a -hon, “USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A,”
  79. (2010). Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation
  80. (2004). Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3 end processing,”
  81. (2009). Phosphorylation of the transcription elongation factor
  82. (2009). Phosphorylation of the yeast Rpb1 C-terminal domain at serines 2,5, and 7,”
  83. (2009). Posttranscriptional processing generates a diversity of 5-modified long and short RNAs,”
  84. (2009). Progression through the RNA Polymerase II
  85. (2009). RAD6-mediated transcription-coupledH2Bubiquitylationdirectlystimulates H3K4 methylation in human cells,”
  86. (2007). Regulation of histone modification and cryptic transcription by the
  87. (2009). RNA polymerase II associated factor 1/PD2 maintains self-renewal by its interaction with
  88. (2002). RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach,”
  89. (2006). RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing,”
  90. (2000). RNA polymerase II elongation through chromatin,”
  91. (2007). Rtf1 is a multifunctional component of the Paf1 complex that regulates gene expression by directing cotranscriptional
  92. (2011). S.J.Anderson,M.L.Sikes,Y.Zhangetal.,“Thetranscription elongation factor Spt5 influences transcription by RNA polymerase I positively and negatively,”
  93. (1997). Schr¨ ock et al., “Advancedstage cervical carcinomas are defined by a recurrent pattern ofchromosomalaberrationsrevealinghighgeneticinstability and a consistent gain of chromosome arm
  94. (2001). Selective recognition of methylated lysine
  95. Serine-7 of the RNA polymerase II CTD is specifically required for snRNA gene expression,”
  96. (1997). SET1, a yeast member of the Trithorax family, functions in transcriptional silencing and diverse cellular processes,”
  97. (2002). Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression,”
  98. (2005). Single-nucleosome mapping of histone modifications in S.
  99. (2002). Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences,”
  100. (1998). Spt5, and Spt6 control transcription elongation by RNA polymerase II
  101. (2003). Structure of an mRNA capping enzyme bound to the phosphorylated carboxy-terminal domain of RNA polymerase
  102. (2000). Synthetic lethal interactions suggestarolefortheSaccharomycescerevisiaeRtf1proteinin transcription elongation,”
  103. (2011). T o m s o n ,C .P .D a v i s ,M .H .W a r n e r ,a n dK .M .A r n d t , “Identification of a role for histone H2B ubiquitylation in noncoding RNA 3-end formation through mutational analysis of
  104. (2003). Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity,”
  105. (2002). Tawiah-Boateng et al., “Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by
  106. (2006). Terminating the transcript: breaking up is hard to do,”
  107. (2009). The basal initiation machinery: beyond the general transcription factors,”
  108. (1999). The chromatin-specific transcription elongation factor
  109. (2000). The chrome domain protein Chd1p from budding yeast is an ATP-dependent chromatin-modifying factor,”
  110. (2003). The establishment, inheritance, and function of silenced chromatin
  111. (2003). The FACT complex travels with elongating RNA polymerase II and is important for the fidelity of transcriptional initiation in vivo,”
  112. (2005). The HRPT2 tumor suppressor gene product parafibromin associates with human
  113. (2006). The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis,”
  114. (2005). The human PAF complex coordinates transcription with events downstream
  115. (2010). The human PAF1 complex acts in chromatin transcription elongation both independently and cooperatively with
  116. (2010). The PAF1 complex component Leo1 is essential for cardiac and neural crest development in zebrafish,”
  117. (2004). The Paf1 complex has functions independent of actively transcribing RNA polymerase
  118. (2003). The Paf1 complex is essential for histone monoubiquitination by the Rad6-Bre1 complex, which signals for histone methylation by COMPASS and
  119. (2009). The Paf1 complex is required for efficient transcription elongation by RNA polymerase
  120. (2003). The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation,”
  121. (2002). The Paf1 complex physically and functionally associates with transcription elongation factors in vivo,”
  122. (2011). The Paf1 complex represses ARG1 transcription in Saccharomyces cerevisiae by promoting histone modifications,”
  123. (2005). The parafibromin tumor suppressor protein is part
  124. (2010). The RNA polymerase-associated factor 1 complex (Paf1C) directly increases the elongation rate of RNA polymerase I and is required for efficient regulation of rRNA synthesis,”
  125. (2007). The role of histone ubiquitylation and deubiquitylation in gene expression as determined by the analysis of an
  126. (2003). The Rtf1 Component of the Paf1 Transcriptional Elongation Complex Is Required for Ubiquitination of Histone H2B,”
  127. (2003). The Set2 histone methyltransferase functions through the phosphorylated carboxyl-terminal domain of RNA polymerase
  128. The transcriptional landscape of the yeast genome defined by RNA sequencing,”Science,vol.320,no.5881,pp.1344–1349,2008.
  129. (2009). The tumor suppressor
  130. (2002). The yeast Paf1-RNA polymerase II complex is required for full expression of a subset of cell cycle-regulated genes,”
  131. (2006). The Yng1p plant homeodomain finger is a methyl-histone binding module that recognizes lysine
  132. (2002). Trans-histone regulatory pathway in chromatin,”
  133. (2010). Transcript elongation by RNA polymerase
  134. (2002). Transcript elongation on a nucleoprotein template,”
  135. (2003). Transcription elongation factors repress transcription initiation from cryptic sites,”
  136. (1991). Transcription on nucleosomal templates by RNA polymerase II in vitro: inhibition of elongation with enhancement of sequence-specific pausing,”
  137. (2009). Transcription termination by nuclear RNA polymerases,”
  138. (2011). Transcriptional activators enhance polyadenylation of mRNA precursors,”
  139. (2006). Transcriptional repression and DNA hypermethylation of a small set of ES cell marker genes in male germline stem cells,”
  140. (2004). Transitions in RNA polymerase II elongation complexes at the 3 ends of genes,”
  141. (2009). Ubiquitination of histone H2B regulates chromatin dynamics by enhancing nucleosome stability,”
  142. (2002). Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast,”
  143. (2011). Unravelling the means to an end: RNA polymerase II transcription termination,”
  144. (2002). Villablanca et al., “HRPT2, encoding parafibromin, is mutated in hyperparathyroidismjaw tumor syndrome,”
  145. (2010). Yatim et al., “HIV-1 Tat Assembles a Multifunctional Transcription Elongation Complex and Stably Associates with the 7SK snRNP,”
  146. (1999). Yeast carboxyl-terminal domain kinase I positively and negatively regulates RNA polymerase II carboxyl-terminal domain phosphorylation,”
  147. (2011). Yeast transcription elongation factor Spt5 associates with RNA polymerase I and RNA polymerase II directly,”
  148. (2009). yFACT induces global accessibility of nucleosomal DNA without H2A-H2B displacement,”
  149. (2006). Yng1 PHD finger binding to H3 Trimethylated at K4 promotes NuA3 HAT a c t i vi tya tK 1 4o fH 3a n dt r a n s c ri p t i o na tas u b s e to ft a r g e t e d ORFs,”

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