Ask about this productRelated genes to: LIN28 antibody
- Gene:
- LIN28A NIH gene
- Name:
- lin-28 homolog A
- Previous symbol:
- LIN28
- Synonyms:
- LIN-28, FLJ12457, ZCCHC1, CSDD1
- Chromosome:
- 1p36.11
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-21
- Date modifiied:
- 2016-10-05
Related products to: LIN28 antibody
Related articles to: LIN28 antibody
- The transition of embryonic stem cells (ESCs) from a pluripotent state to lineage commitment is governed by complex regulatory mechanisms, including chromatin remodeling, as well as transcriptional and post-transcriptional processes. Recent studies have emphasized the interplay between these mechanisms, revealing intricate, multilayered regulatory networks that require further elucidation. In this study, we reveal a new connection between the RNA-binding protein LIN28A and the epigenetic regulation of ESC differentiation. LIN28A is upregulated during the early stages of neural commitment and undergoes a shift in subcellular localization from the nucleus to the cytoplasm upon differentiation. Generation and analysis of Lin28a knockout (KO) ESCs revealed that, although these cells can self-renew, they exhibit a pronounced defect in differentiating into neural precursors. However, mesodermal and endodermal differentiation proceeds normally in Lin28a KO cells, suggesting a neuronal-specific function for LIN28A. Proteomic analyses revealed a dynamic, context-dependent LIN28A interactome, with distinct sets of putative interacting partners in ESCs compared to those in differentiating cells. Among the ESC-specific putative interactors, we validated an RNA-dependent association of LIN28A with components of Polycomb Repressive Complex 2 (PRC2), a key chromatin-modifying complex that deposits the repressive histone modification H3K27me3. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) demonstrated that loss of LIN28A results in persistent PRC2 occupancy at the promoters of developmental genes, accompanied by partial uncoupling between PRC2 binding and H3K27me3 deposition. Lin28a KO causes differentiation defects that are not rescued by pharmacological inhibition of PRC2 enzymatic activity, suggesting that LIN28A regulates PRC2 chromatin dynamics independently of H3K27me3 deposition. Furthermore, we identified an interaction between LIN28A and the long non-coding RNA Neat1, which may serve as a scaffold facilitating PRC2 eviction from chromatin. Taken together, our findings reveal a previously unrecognized role for LIN28A in regulating PRC2-mediated chromatin dynamics and underscore its importance in epigenetic control of neuronal differentiation. - Source: PubMed
Publication date: 2026/05/05
Piscitelli SilviaCascone EmanuelaD'Ambrosio ChiaraDivisato GiuseppinaGiannino EmiliaDe Lisio LauraLeoni GuidoD'Andrea DanielMatassa Danilo SwannLanzuolo ChiaraRosti ValentinaZizolfi Maria ChiaraMatuozzo Monicadi Patrizio Soldateschi EmanueleMaiuri PaoloScaloni AndreaPassaro FabianaParisi Silvia - The microRNA miR-124 promotes neuronal identity by acting globally, through its multiple targets, at the epigenetic, transcriptional and post-transcriptional levels. We have previously shown that miR-124 acts as a potent driver of the astrocytic fate switch toward an immature neuronal identity, while its supplementation with the neurogenic compound ISX9 enhances in vitro neuronal maturation. Nevertheless, additional cues are needed to enhance the in vivo neurogenic reprogramming capacity of miR-124/ISX9 following neurodegeneration or neurotrauma. In this study, we constructed the core transcriptional regulatory network regulated by miR-124 and ISX9 during astrocyte-to-neuron conversion. Our analysis revealed that the DNA demethylase TET1 is a pivotal transcriptional regulator of the miR-124/ISX9 neurogenic reprogramming process. Silencing of Tet1 impaired the miR-124-mediated neuronal conversion of astrocytes, as well as the ISX9-reinforced differentiation of iNs. We also identified the DNA/RNA binding protein LIN28A as the top mediator of ISX9 neurogenic action and provide evidence that it acts as a coregulator of the expression of synaptic genes, along with TET1. Taken together, our data suggest that TET1 and LIN28A are potent candidates for amplifying miR-124/ISX9 combined in vivo reprogramming action and enhance iNs' differentiation state. - Source: PubMed
Publication date: 2026/04/25
Papadimitriou ElsaIohan Lukas daCCFrazeskou AlexandraXingi EvangeliaCosta Marcos RThomaidou Dimitra - Spermatogonial differentiation is a key step in spermatogenesis, yet the transcriptional programs that control this process are not fully defined. E4f1 has been reported to be essential for embryonic development, mitochondrial function and spermatogonial stem cell (SSC) maintenance in mice. However, its function in spermatogonial differentiation and meiosis progression is unknown. - Source: PubMed
Publication date: 2026/04/14
Wang Fei-ChenHe ZhenYan Rong-GeWang Yu-JunWu Jia-LuYang Qi-En - - Source: PubMed
Publication date: 2026/04/13
Chae Hee YoungYi KyungrimLim Su-GeunPark Ji YeongHyung HyejinKim Si-YongKim WanilLee Sang-IlChoi Dong KyuKim Myoung OkRyoo Zae YoungKo JiwonJang Soyeon - Effective therapies for liver fibrosis are lacking. The RNA-binding protein Lin28A is upregulated in human cirrhotic and mouse fibrotic livers, where it localizes to activated hepatic stellate cells (HSCs). HSCs-specific overexpression of Lin28A worsened carbon tetrachloride (CCl)-induced fibrosis in mice. In LX-2 and primary mouse HSCs, Lin28A knockdown suppressed activation and induced hallmarks of ferroptosis, including mitochondrial damage, lipid peroxidation, and glutathione depletion. Mechanistically, Lin28A repressed the maturation of let-7 microRNAs, leading to increased expression of its target, high-mobility group AT-hook 2 (HMGA2). HMGA2, alongside hypoxia-inducible factor-1α (HIF-1α), contributed to the downregulation of the ferroptosis defense proteins SLC7A11 and GPX4. Notably, the anti-fibrotic effects of the Lin28A inhibitor C1632 were dependent on ferroptosis induction, as co-treatment with ferrostatin-1 reversed its impact on HSCS activation and death. In vivo, C1632 treatment alleviated CCl-induced liver fibrosis. These results identify Lin28A as a regulator of HSCS ferroptosis and a potential target for anti-fibrotic therapy. - Source: PubMed
Publication date: 2026/03/16
Wang AnkangSun HongfaZhao HaixiaXie YeYan MengchaoZhang YueSong XiaojingDing FanghuiChai ChangpengNi HaixuYao JiaLi Xun