Details

Autor(en) / Beteiligte

• Choudhury, Rupam
• Singh, Sukhdeep
• Arumugam, Senthil
• Roguev, Assen
• Stewart, A Francis

Titel

The Set1 complex is dimeric and acts with Jhd2 demethylation to convey symmetrical H3K4 trimethylation

Ist Teil von

• Genes & development, 2019-05, Vol.33 (9-10), p.550-564

Ort / Verlag

United States: Cold Spring Harbor Laboratory Press

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Epigenetic modifications can maintain or alter the inherent symmetry of the nucleosome. However, the mechanisms that deposit and/or propagate symmetry or asymmetry are not understood. Here we report that yeast Set1C/COMPASS (complex of proteins associated with Set1) is dimeric and, consequently, symmetrically trimethylates histone 3 Lys4 (H3K4me3) on promoter nucleosomes. Mutation of the dimer interface to make Set1C monomeric abolished H3K4me3 on most promoters. The most active promoters, particularly those involved in the oxidative phase of the yeast metabolic cycle, displayed H3K4me2, which is normally excluded from active promoters, and a subset of these also displayed H3K4me3. In wild-type yeast, deletion of the sole H3K4 demethylase, Jhd2, has no effect. However, in monomeric Set1C yeast, Jhd2 deletion increased H3K4me3 levels on the H3K4me2 promoters. Notably, the association of Set1C with the elongating polymerase was not perturbed by monomerization. These results imply that symmetrical H3K4 methylation is an embedded consequence of Set1C dimerism and that Jhd2 demethylates asymmetric H3K4me3. Consequently, rather than methylation and demethylation acting in opposition as logic would suggest, a dimeric methyltransferase and monomeric demethylase cooperate to eliminate asymmetry and focus symmetrical H3K4me3 onto selected nucleosomes. This presents a new paradigm for the establishment of epigenetic detail.