RRC ID 35974
著者 Oswald F, Rodriguez P, Giaimo BD, Antonello ZA, Mira L, Mittler G, Thiel VN, Collins KJ, Tabaja N, Cizelsky W, Rothe M, Kühl SJ, Kühl M, Ferrante F, Hein K, Kovall RA, Dominguez M, Borggrefe T.
タイトル A phospho-dependent mechanism involving NCoR and KMT2D controls a permissive chromatin state at Notch target genes.
ジャーナル Nucleic Acids Res
Abstract The transcriptional shift from repression to activation of target genes is crucial for the fidelity of Notch responses through incompletely understood mechanisms that likely involve chromatin-based control. To activate silenced genes, repressive chromatin marks are removed and active marks must be acquired. Histone H3 lysine-4 (H3K4) demethylases are key chromatin modifiers that establish the repressive chromatin state at Notch target genes. However, the counteracting histone methyltransferase required for the active chromatin state remained elusive. Here, we show that the RBP-J interacting factor SHARP is not only able to interact with the NCoR corepressor complex, but also with the H3K4 methyltransferase KMT2D coactivator complex. KMT2D and NCoR compete for the C-terminal SPOC-domain of SHARP. We reveal that the SPOC-domain exclusively binds to phosphorylated NCoR. The balance between NCoR and KMT2D binding is shifted upon mutating the phosphorylation sites of NCoR or upon inhibition of the NCoR kinase CK2β. Furthermore, we show that the homologs of SHARP and KMT2D in Drosophila also physically interact and control Notch-mediated functions in vivo Together, our findings reveal how signaling can fine-tune a committed chromatin state by phosphorylation of a pivotal chromatin-modifier.
巻・号 44(10)
ページ 4703-20
公開日 2016-6-2
DOI 10.1093/nar/gkw105
PII gkw105
PMID 26912830
PMC PMC4889922
MeSH Animals Casein Kinase II / metabolism Cell Line Cell Line, Tumor Chromatin / metabolism* Co-Repressor Proteins / metabolism* DNA-Binding Proteins Drosophila Proteins / genetics Drosophila Proteins / metabolism Gene Expression Regulation* Histone Code Histone-Lysine N-Methyltransferase Homeodomain Proteins / chemistry Homeodomain Proteins / metabolism Humans Mice Myeloid-Lymphoid Leukemia Protein / metabolism* Nuclear Proteins / chemistry Nuclear Proteins / metabolism* Phosphorylation Protein Interaction Domains and Motifs RNA-Binding Proteins Receptors, Notch / metabolism* Transcription, Genetic* Xenopus laevis
IF 11.502
引用数 30
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ショウジョウバエ 18497R-1 18497R-4