title: Protein interactions within the Set1 complex and their roles in the regulation of histone 3 lysine 4 methylation.
abstract: Set1 is the catalytic subunit and the central component of the evolutionarily conserved Set1 complex (Set1C) that methylates histone 3 lysine 4 (H3K4). Here we have determined protein/protein interactions within the complex and related the substructure to function. The loss of individual Set1C subunits differentially affects Set1 stability, complex integrity, global H3K4 methylation, and distribution of H3K4 methylation along active genes. The complex requires Set1, Swd1, and Swd3 for integrity, and Set1 amount is greatly reduced in the absence of the Swd1-Swd3 heterodimer. Bre2 and Sdc1 also form a heteromeric subunit, which requires the SET domain for interaction with the complex, and Sdc1 strongly interacts with itself. Inactivation of either Bre2 or Sdc1 has very similar effects. Neither is required for complex integrity, and their removal results in an increase of H3K4 mono- and dimethylation and a severe decrease of trimethylation at the 5' end of active coding regions but a decrease of H3K4 dimethylation at the 3' end of coding regions. Cells lacking Spp1 have a reduced amount of Set1 and retain a fraction of trimethylated H3K4, whereas cells lacking Shg1 show slightly elevated levels of both di- and trimethylation. Set1C associates with both serine 5- and serine 2-phosphorylated forms of polymerase II, indicating that the association persists to the 3' end of transcribed genes. Taken together, our results suggest that Set1C subunits stimulate Set1 catalytic activity all along active genes.
authors.affiliation: Laboratoire d'InstabilitéduGénome et Cancérogénèse, Institut de Biologie Structurale et Microbiologie, CNRS, Marseille 13402, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Dehé
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dichtl
authors.forename: Daniel
authors.initials: D
authors.lastname: Schaft
authors.forename: Assen
authors.initials: A
authors.lastname: Roguev
authors.forename: Mercè
authors.initials: M
authors.lastname: Pamblanco
authors.forename: Régine
authors.initials: R
authors.lastname: Lebrun
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rodríguez-Gil
authors.forename: Msau
authors.initials: M
authors.lastname: Mkandawire
authors.forename: Katarina
authors.initials: K
authors.lastname: Landsberg
authors.forename: Anna
authors.initials: A
authors.lastname: Shevchenko
authors.forename: Andrej
authors.initials: A
authors.lastname: Shevchenko
authors.forename: Lorena E
authors.initials: LE
authors.lastname: Rosaleny
authors.forename: Vicente
authors.initials: V
authors.lastname: Tordera
authors.forename: Sebastián
authors.initials: S
authors.lastname: Chávez
authors.forename: A Francis
authors.initials: AF
authors.lastname: Stewart
authors.forename: Vincent
authors.initials: V
authors.lastname: Géli
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D011485:Protein Binding; D021122:Protein Subunits; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; D008239:Lysine