{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nFGF16 was first characterized through cloning and expression studies that revealed a high degree of evolutionary conservation between mouse and human transcripts and a predominant expression in cardiac tissue. Detailed promoter analyses further identified cardiac‐specific regulatory elements—such as a MEF2 binding site—coupled with chromatin remodeling events that ensure its selective transcription in the postnatal heart ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ").\n\nFunctional investigations have demonstrated that FGF16 plays a critical role in heart development and repair. During embryogenesis, it promotes myocardial growth, proper trabeculation, and cardiomyocyte proliferation, while its deficiency leads to chamber dilation, wall thinning, and reduced cell numbers. In the neonatal and postnatal heart, FGF16 not only supports regeneration by enhancing cardiomyocyte replication but also appears to counteract adverse remodeling—acting, at least in part, by antagonizing FGF2-induced TGF-β1 signaling to mitigate hypertrophy and fibrosis ("}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "8"}]}, {"type": "t", "text": ").\n\nAn additional regulatory dimension has been revealed in studies showing that post-transcriptional m6A modification—mediated by the methyltransferase Mettl3 and its effector Ythdf2—negatively regulates FGF16 mRNA levels. This m6A-dependent pathway modulates cardiomyocyte proliferation and is essential for efficient heart regeneration following injury ("}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ").\n\nOutside of cardiac biology, FGF16 is transiently expressed in the developing inner ear, where its localization in the otic cup and vesicle suggests a role in sensory epithelial patterning, even though its ablation does not produce overt defects in otic development. Moreover, overexpression studies have implicated FGF16 in metabolic regulation by inducing brown adipose tissue–like features in white fat depots and altering bile acid metabolism, although these systemic effects appear to be complex and multifactorial ("}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": ").\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "David P Sontag, Peter A Cattini "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and bacterial expression of postnatal mouse heart FGF-16."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12619867"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12619867"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alina G Sofronescu, Yan Jin, Peter A Cattini "}, {"type": "b", "children": [{"type": "t", "text": "A myocyte enhancer factor 2 (MEF2) site located in a hypersensitive region of the FGF16 gene locus is required for preferential promoter activity in neonatal cardiac myocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/dna.2007.0689"}], "href": "https://doi.org/10.1089/dna.2007.0689"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18260768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18260768"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shun Yan Lu, Farah Sheikh, Patricia C Sheppard, et al. 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