{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HDGFL2 (also known as HRP2 or HDGF‐related protein 2) is an evolutionarily conserved chromatin‐associated factor that participates in multiple key cellular processes. Its domain organization closely resembles that of LEDGF/p75, including an integrase binding domain that enables HDGFL2 to interact directly with HIV integrase and stimulate its enzymatic activity. Through this interaction, HDGFL2 can promote efficient and properly targeted integration of the HIV genome into host chromatin, especially under conditions where LEDGF/p75 is absent or depleted."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in HIV integration, HDGFL2 binds to methylated histone marks via its PWWP domain. This dual capacity to interact with both nucleosomal DNA and modified histone tails underlies its involvement in transcriptional regulation, ensuring proper transcription elongation and gene expression. In particular, HDGFL2 has been implicated in directing chromatin remodeling through partnerships with factors such as DPF3a and components of BAF complexes during myogenic differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, HDGFL2 contributes to genome stability by facilitating homologous recombination repair; it aids in the recruitment of DNA end resection factors (for example, CtIP) to double‐strand breaks, thereby promoting the repair process."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Its misregulation is also linked to cancer progression. Overexpression of HDGFL2 has been associated with enhanced tumor cell growth in hepatocellular carcinoma and has been shown to contribute to chemoresistance in multiple myeloma by modulating epigenetic marks and gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, genetic studies in mice reveal that while loss of HDGFL2 alone is tolerated, dual deficiency with LEDGF/p75 results in embryonic lethality accompanied by developmental defects, underscoring their complementary roles in development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, HDGFL2 acts as a multifunctional adaptor that links chromatin to various effector processes. It contributes to HIV-1 integration, transcription regulation, chromatin remodeling, and DNA repair, and its dysregulation bears significant implications for oncogenesis and cellular stress responses.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Peter Cherepanov, Eric Devroe, Pamela A Silver, et al. 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