| 1. |
- Davydova, Erna, et al.
(author)
-
The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes
- 2021
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where “x” is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.
|
|
| 2. |
- Ravasi, Timothy, et al.
(author)
-
An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man
- 2010
-
In: CELL. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 140:5, s. 744-752
-
Journal article (peer-reviewed)abstract
- Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.
|
|
