Ask about this productRelated genes to: Cited4 antibody
- Gene:
- CITED4 NIH gene
- Name:
- Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 4
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 1p34.2
- Locus Type:
- gene with protein product
- Date approved:
- 2002-05-29
- Date modifiied:
- 2016-10-05
Related products to: Cited4 antibody
Related articles to: Cited4 antibody
- Tail docking, serving as an important management intervention in animal husbandry, plays a significant role in regulating tail fat deposition and improving production performance and health status in fat-tailed sheep. This study systematically revealed the reprogramming effects of tail docking on the epigenetic landscape and transcriptome of fat-tailed sheep by integrating whole-genome bisulfite sequencing (WGBS) and RNA m6A methylated immunoprecipitation sequencing (MeRIP-seq). At the DNA level, the tail-docked group exhibited a pronounced trend of hypomethylation across multiple functional genomic regions, including promoters, exons, and introns. Differentially methylated regions (DMRs) were significantly enriched in pathways related to tissue development and stress response, such as the Hippo signaling pathway and adherens junctions. Pyrosequencing validation of the promoter region of the key gene DGAT1 further confirmed the reliability of the WGBS data. At the RNA level, RNA m6A modifications showed an overall up-regulated pattern: the tail-docked group displayed higher numbers of m6A peaks, greater total peak length, and increased genomic coverage compared to the control group, along with better overall prediction of modification sites. Genes associated with differential m6A peaks were closely related to processes such as stem cell pluripotency and cytoskeleton regulation. qPCR validation of several methylation-related enzyme genes (e.g., METTL3, FTO, YTHDF1) yielded results consistent with the sequencing trends. Through integrated analysis of DNA methylation and RNA methylation, we identified 143 genes with concurrent changes in methylation and mRNA expression, among which 41 genes were regulated by both DNA and RNA methylation. These genes were primarily enriched in the adherens junction pathway. Notably, two core genes CITED4 and ZNF644 showed significant changes across all three levels: DNA methylation, RNA methylation, and mRNA expression. This study systematically elucidates the epigenetic mechanism by which tail docking stress induces coordinated DNA hypo-methylation and RNA m6A hyper-methylation to regulate transcriptomic reprogramming in response to environmental intervention. The findings provide novel insights into the molecular basis of trait formation in livestock. - Source: PubMed
Publication date: 2026/02/04
Zhang JianMa YannanSong Shuzhen - Recent advances in predicting and modeling conformational ensembles of intrinsically disordered proteins (IDPs) have provided much needed insights into sequence-ensemble relationships. It is thought that conservation of physicochemical properties, but not the exact identity or order of the amino acids, maintains IDP ensemble properties that are crucial for function. However, detailed experimental studies are still required to fully understand the relationships between sequence and function in IDPs. The human CITED proteins, which are fully disordered transcriptional regulators, share conserved C-terminal transactivation domains (CTADs) that interact with the TAZ1 domain of the transcriptional coactivators CBP/p300. The conserved CTADs harbor amino acid substitutions in regions that are known to be important for interactions of CITED2 with TAZ1, but the effects of these substitutions on TAZ1 binding for the other CITED proteins are unknown. Here, we use solution NMR spectroscopy, circular dichroism, and surface plasmon resonance to characterize the conformational ensembles, dynamics, and interactions of the CITED CTADs. The CTADs are disordered in isolation, although the CITED2 CTAD uniquely displays residual helical structure that is sensitive to ionic strength and protein concentration. In contrast, the CITED1 and CITED4 CTADs remain largely disordered and exhibit more uniform dynamics. Quantitative binding measurements reveal differences in thermodynamics and kinetics for the CTADs' interactions with TAZ1, with CITED2 binding most tightly and CITED4 exhibiting significantly weaker affinity. Our results highlight the sensitivity of IDP conformational ensembles to minor sequence changes and the impacts that changes in IDP structures and dynamics can have on biological functions. - Source: PubMed
Publication date: 2026/01/21
Do To UyenKraft Emma JChappell Garrett FParnham StuartBerlow Rebecca B - The CITED proteins function as transcriptional modulators that are essential for vertebrate development. These proteins interact with numerous partners, notably transcription factors and co-activators. The hallmark of the CITED family is their conserved carboxy-terminal domain, which interacts strongly with the CBP/p300 co-activators. The expression of CITED genes is detected early during embryogenesis within embryonic and foetal regions critical for cardiac morphogenesis, among other developmental processes. Notably, CITED2 loss of function is strongly associated with congenital heart malformations in mice and zebrafish embryos, as well as congenital heart disease (CHD) in humans, whereas other CITED family members are not critical for cardiogenesis. Emerging evidence implicates CITED2 and CITED4 in regulating heart physiological adaptations and protective responses to pathological stress. This review provides a detailed analysis of CITED proteins and their interactors, focusing on CITED-target genes relevant for cardiogenesis and heart disease. We also highlight recent findings indicating that CITED2 and CITED4 may be instrumental for the development of novel therapeutic strategies to mitigate CHD and preserve adult cardiac function. - Source: PubMed
Publication date: 2025/11/07
Bragança JoséCabrita Pinto Rute LuísaVentura IgorFerreira SilvanaMarreiros António - Cardiac physiological growth is needed for increased demands of heart function after exercise. Prior work suggests that exercise-responsive molecules, including Cbp/P300 Interacting Transactivator with Glu/Asp Rich Carboxy-Terminal Domain 4 (CITED4), can mediate exercise-induced myocardial physiological growth and promote functional recovery after ischemia-reperfusion injury in adult mice. Moreover, forced expression of CITED4 induces physiological cardiac growth in rodent model. Multiple mouse models of myocardial physiological growth have been established by activating genes such as CITED4, IGF1R and AKT. However, an in vitro model of physiological growth in cardiomyocytes derived from human embryonic stem cells (hESC-CMs) has not yet been developed. To provide clinically relevant models for exploring the molecular mechanism of physiological growth, we generated an inducible hESC cell line with forced CITED4 gene expression and differentiated those hESCs towards cardiomyocytes. The results showed that forced CITED4 expression increased cell size and proliferation in hESC-CMs, and promoted cardiomyocyte proliferation in 3D cardiac microtissues. Activation of protein kinase B (also known as AKT1) signaling was necessary for CITED4-induced proliferation in hESC-CMs and 3D cardiac microtissues, while mTOR signaling mediated both proliferation and physiological hypertrophy induced by CITED4. In an in vitro model mimicking ischemia-reperfusion injury, CITED4 expression inhibited cardiomyocyte apoptosis in hESC-CMs and 3D cardiac microtissues, and this effect was mediated by activation of the mTOR signaling. In conclusion, we successfully generate a physiological growth model in hESC-CMs and 3D cardiac microtissues. Moreover, physiological growth induced by CITED4 is mediated by activation of the mTOR signaling, which is necessary to promote both proliferation and physiological hypertrophy, and to alleviate apoptosis after ischemia-reperfusion injury in hESC-CMs and 3D cardiac microtissues. - Source: PubMed
Publication date: 2025/10/30
Liu ChangYao JianhuaWu XinyingGuo JingZhan QingyiZhu YujiaoChatterjee EmeliKeswani TarunMeng DanniLi GuopingCretoiu DragosRosenzweig AnthonyBei YihuaXiao Junjie - The role of epitranscriptomic changes in the development of acquired endocrine therapy (ET)- resistance in estrogen receptor α (ER) expressing breast cancer (BC) is unknown. We tested the hypothesis that inhibition of METTL3, the methyltransferase responsible for the mRNA modification N-6 methyladenosine (m6A), alters m6A modifications and differentially regulates the abundance of mRNA transcripts in ET-sensitive MCF-7 versus resistant LCC9 ER + human BC cells. Differential m6A modifications were identified using direct mRNA sequencing (DRS) performed on five replicates for each cell line ± 1 µM STM2457, a selective METTL3 inhibitor, using Nanopore MinION long read RNA-seq. Parallel short read Illumina RNA-seq quantified differential transcript abundance in the same samples. Selected results were validated by RT-qPCR, m6A-RIP-qPCR, reporter assays, and western blot analysis. Statistical analysis combined m6Anet, a machine-learning algorithm designed to call m6A modified bases, with a generalized linear model following a binomial distribution analysis to identify significant differential m6A modification ratios (DMR). Distinct METTL3 dependent m6A modification patterns in LCC9 and MCF-7 cells were observed in differentially expressed genes (DEG) associated with ET-resistance, including EEF1A2, ACTB, FLNA, PDIA6, AMIGO2, TPT1, XBP1, and CITED4. Select results were validated in additional ET-resistant BC cell lines. m6A-RIP-RT-qPCR validated specific m6A sites. We examined the proximity of m6A sites to estrogen receptor α (ER α)-mRNA binding sites reported in MCF-7 cells. ACTB, PDIA6, and XBP1 demonstrated a short-range proximity, with m6A sites located within 100 bp of ERα binding sites, suggesting a role for m6A in influencing ERα-mRNA binding. Our work provides a framework for integrating DRS and DEG omics data. Our results suggest a role for dysregulation of m6A modifications in pathways implicated in ET resistance in BC. - Source: PubMed
Publication date: 2025/07/09
Petri Belinda JPiell Kellianne MAvila-Valdes Bailey LStanley Christian GWinkler Laura JBrown Johnny TylerUlett RyeSanchez GabrielaChariker Julia HRouchka Eric CKlinge Carolyn M