Background: The normal cardiac rhythm is generated in the sinoatrial node (SAN). Changes in ionic currents of the SAN may cause sinus arrhythmia. CXXC finger protein 1 (Cfp1) is an epigenetic regulator that is involved in transcriptional regulation of multiple genes.
Objective: The purpose of this study was to explore whether Cfp1 controls SAN function through regulation of ion channel-related genes.
Methods: Electrophysiological study, patch clamp recording, reverse transcriptase polymerase chain reaction, optical mapping, chromatin immunoprecipitation, and immunofluorescence staining were performed to evaluate the function of SAN and underlying mechanism on Cfp1 heterozygous knockout (Cfp1) mice.
Results: Heart rate was slower slightly and SAN recovery time was longer in Cfp1 mice than controls. Whole-cell patch-clamp recording showed that the firing rate of action potentials was reduced in Cfp1 mice. The density of I current was reduced by 66% in SAN cells of Cfp1 mice but the densities of I, I, and I were not changed. The hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) mRNA level in SAN tissue of Cfp1 mice was reduced. The HCN4 protein was significantly decreased in SAN cells and tissues after heterozygous deletion of Cfp1. Chromatin immunoprecipitation assay on cultured HL-1 cells demonstrated that Cfp1 was enriched in the promoter regions of HCN4. Knockdown of Cfp1 reduced H3K4 trimethylation, H3K9 acetylation, and H3K27 acetylation of HCN4 promoter region.
Conclusion: Deficiency of Cfp1 leads to small changes in heart rate by moderate epigenetic modification alterations and significant protein downregulation of HCN4 ion channels in mice.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.hrthm.2021.06.1190 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Histone lysine methyltransferases and their specific methylation marks show significant changes in mouse testes from young to older ages.
Biogerontology
January 2025
Department of Histology and Embryology, Akdeniz University School of Medicine, Campus, 07070, Antalya, Türkiye.
Spermatogenesis is finely regulated by histone methylation, which is crucial for regulating gene expression and chromatin remodeling. Functional studies have demonstrated that the histone lysine methyltransferases (KMTs) SETD1B, CFP1, SETDB1, G9A, and SETD2 play pivotal roles in spermatogenesis through establishing the key histone methylation marks, H3K4me3, H3K9me2, H3K9me3, and H3K36me3, respectively. This study aimed to evaluate the spatiotemporal expression of these KMTs and methylation marks as well as senescence-associated β-galactosidase (β-GAL), transcriptional activity, and apoptosis rates in mouse testes during biological aging.
View Article and Find Full Text PDFCfp1 Controls Cardiomyocyte Maturation by Modifying Histone H3K4me3 of Structural, Metabolic, and Contractile Related Genes.
Adv Sci (Weinh)
March 2024
Department of Pharmacology (State Key Laboratory of Frigid Zone Cardiovascular Disease, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150086, P. R. China.
Article Synopsis
- Cardiomyocyte maturation is essential for heart development, and abnormal maturation can lead to serious heart diseases, with Cfp1 being an under-researched factor in this process.
- The study found that cardiomyocyte-specific Cfp1 knockout mice died within four weeks due to inhibited maturation, whereas Cfp1 transgenic mice and hiPSC-CMs with Cfp1 overexpression exhibited a more mature phenotype.
- Cfp1 affects gene expression crucial for cardiomyocyte maturation by regulating H3K4me3 histone modification, indicating that its dysfunction is closely linked to cardiac diseases.
CFP1 governs uterine epigenetic landscapes to intervene in progesterone responses for uterine physiology and suppression of endometriosis.
Nat Commun
June 2023
Department of Biomedical Science, CHA University, Seongnam, Gyeonggi, 13488, Korea.
Progesterone (P) is required for the preparation of the endometrium for a successful pregnancy. P resistance is a leading cause of the pathogenesis of endometrial disorders like endometriosis, often leading to infertility; however, the underlying epigenetic cause remains unclear. Here we demonstrate that CFP1, a regulator of H3K4me3, is required for maintaining epigenetic landscapes of P-progesterone receptor (PGR) signaling networks in the mouse uterus.
View Article and Find Full Text PDFEpigenetic regulator Cfp1 safeguards male meiotic progression by regulating meiotic gene expression.
Exp Mol Med
August 2022
Department of Stem Cell and Regenerative Biotechnology, Humanized Pig Center, Konkuk University, Seoul, 05029, Republic of Korea.
Meiosis occurs specifically in germ cells to produce sperm and oocytes that are competent for sexual reproduction. Multiple factors are required for successful meiotic entry, progression, and termination. Among them, trimethylation of histone H3 on lysine 4 (H3K4me3), a mark of active transcription, has been implicated in spermatogenesis by forming double-strand breaks (DSBs).
View Article and Find Full Text PDFExpression of the histone lysine methyltransferases SETD1B, SETDB1, SETD2, and CFP1 exhibits significant changes in the oocytes and granulosa cells of aged mouse ovaries.
Histochem Cell Biol
July 2022
Department of Histology and Embryology, Akdeniz University School of Medicine, Campus, 07070, Antalya, Turkey.
Histone methylation is one of the main epigenetic mechanisms by which methyl groups are dynamically added to the lysine and arginine residues of histone tails in nucleosomes. This process is catalyzed by specific histone methyltransferase enzymes. Methylation of these residues promotes gene expression regulation through chromatin remodeling.
View Article and Find Full Text PDFWant 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!