Set1C is a histone methyltransferase playing an important role in yeast gene regulation. Modeling the structure of this eight-subunit protein complex is an important open problem to further elucidate its functional mechanism. Recently, there has been progress in modeling of larger complexes using constraints to restrict the combinatorial explosion in binary docking of subunits. Here, we model the subunits of Set1C and develop a constraint-based docking approach, which uses high-quality protein interaction as well as functional data to guide and constrain the combinatorial assembly procedure. We obtained 22 final models. The core complex consisting of the subunits Set1, Bre2, Sdc1 and Swd2 is conformationally conserved in over half of the models, thus, giving high confidence. We characterize these high-confidence and the lower confidence interfaces and discuss implications for the function of Set1C.

Download full-text PDF

Source
http://dx.doi.org/10.1002/pmic.201000283DOI Listing

Publication Analysis

Top Keywords

histone methyltransferase
8
constraint-based docking
8
structural modeling
4
modeling histone
4
methyltransferase complex
4
set1c
4
complex set1c
4
set1c saccharomyces
4
saccharomyces cerevisiae
4
cerevisiae constraint-based
4

Similar Publications

Epigenetic abnormalities play a critical role in colon carcinogenesis, making them a promising target for therapeutic interventions. In this study, we demonstrated that curcumin reduces colon cancer cell survival and that a decrease in lysine methylation was involved in such an effect. This correlated with the downregulation of methyltransferases EZH2, MLL1, and G9a, in both wild-type p53 (wtp53) HCT116 cells and mutant p53 (mutp53) SW480 cells, as well as SET7/9 specifically in wtp53 HCT116 cells.

View Article and Find Full Text PDF

Breast cancer (BC) subtypes exhibit distinct epigenetic landscapes, with triple-negative breast cancer (TNBC) lacking effective targeted therapies. This study investigates histone biomarkers and therapeutic vulnerabilities across BC subtypes. The immunohistochemical profiling of >20 histone biomarkers, including histone modifications, modifiers, and oncohistone mutations, was conducted on a discovery cohort and a validation cohort of BC tissues, healthy controls, and cell line models.

View Article and Find Full Text PDF

Abnormal development of the second heart field significantly contributes to congenital heart defects, often caused by disruptions in tightly regulated molecular pathways. , a gene encoding a protein with SET and MYND domains, is essential for heart and skeletal muscle development. Mutations in SMYD1 result in severe cardiac malformations and misregulation of expression in mammals.

View Article and Find Full Text PDF

Small interfering RNA (siRNA) therapy in acute myeloid leukemia (AML) is a promising strategy as the siRNA molecule can specifically target proteins involved in abnormal cell proliferation. The development of a clinically applicable method for delivering siRNA molecules is imperative due to the challenges involved in effectively delivering the siRNA into cells. We investigated the delivery of siRNA to AML MOLM-13 cells with the use of two lipid-substituted polyethyleneimines (PEIs), a commercially available reagent (Prime-Fect) and a recently reported reagent with improved lipid substitution (PEI1.

View Article and Find Full Text PDF

Epigenetics encompasses reversible and heritable genomic changes in histones, DNA expression, and non-coding RNAs that occur without modifying the nucleotide DNA sequence. These changes play a critical role in modulating cell function in both healthy and pathological conditions. Dysregulated epigenetic mechanisms are implicated in various diseases, including cardiovascular disorders, neurodegenerative diseases, obesity, and mainly cancer.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!