RT Journal Article
T1 Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA
A1 Cui, Huanhuan
A1 Schlesinger, Jenny
A1 Schoenhals, Sophia
A1 Tönjes, Martje
A1 Dunkel, Ilona
A1 Meierhofer, David
A1 Cano, Elena
A1 Schulz, Kerstin
A1 Berger, Michael F.
A1 Haack, Timm
A1 Abdelilah-Seyfried, Salim
A1 Bulyk, Martha L.
A1 Sauer, Sascha
A1 Sperling, Silke R.
K1 Corazón - Enfermedades
AB DPF3 (BAF45c) is a member of the BAF chromatin remodeling complex. Two isoforms have been described, namely DPF3a and DPF3b. The latter binds to acetylated and methylated lysine residues of histones. Here, we elaborate on the role of DPF3a and describe a novel pathway of cardiac gene transcription leading to pathological cardiac hypertrophy. Upon hypertrophic stimuli, casein kinase 2 phosphorylates DPF3a at serine 348. This initiates the interaction of DPF3a with the transcriptional repressors HEY, followed by the release of HEY from the DNA. Moreover, BRG1 is bound by DPF3a, and is thus recruited to HEY genomic targets upon interaction of the two components. Consequently, the transcription of downstream targets such as NPPA and GATA4 is initiated and pathological cardiac hypertrophy is established. In human, DPF3a is significantly upregulated in hypertrophic hearts of patients with hypertrophic cardiomyopathy or aortic stenosis. Taken together, we show that activation of DPF3a upon hypertrophic stimuli switches cardiac fetal gene expression from being silenced by HEY to being activated by BRG1. Thus, we present a novel pathway for pathological cardiac hypertrophy, whose inhibition is a long-term therapeutic goal for the treatment of the course of heart failure.
PB Oxford Academic
YR 2016
FD 2016-04-07
LK https://hdl.handle.net/10630/45346
UL https://hdl.handle.net/10630/45346
LA eng
NO Cui, H., Schlesinger, J., Schoenhals, S., Tönjes, M., Dunkel, I., Meierhofer, D., Cano, E., Schulz, K., Berger, M. F., Haack, T., Abdelilah-Seyfried, S., Bulyk, M. L., Sauer, S., & Sperling, S. R. (2016). Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA. Nucleic acids research, 44(6), 2538–2553. https://doi.org/10.1093/nar/gkv1244
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 1 mar 2026