{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSIN3B functions as a master transcriptional scaffold that organizes histone deacetylase complexes to mediate chromatin remodeling and transcriptional repression. Studies of the subnuclear localization of human SIN3B and its association with repressor proteins such as the ETO family indicate that SIN3B is positioned to interact with a diverse array of transcription factors and corepressor partners, thereby fine‐tuning gene silencing events. Biochemical investigations have revealed that a mammalian complex containing SIN3B localizes near gene promoters—approximately 1 kb downstream of transcription start sites—and acts to restrain RNA polymerase II progression, contributing to the re-establishment of repressive chromatin structures. Structural characterizations of the SIN3B protein have further detailed its conserved paired amphipathic helix (PAH) domains that confer binding specificity to factors such as REST and have delineated how SIN3B physically encircles HDAC enzymes, contacting critical allosteric regions to stimulate deacetylase catalysis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cellular stress and oncogenic signals, SIN3B plays a pivotal role in controlling cell fate. Genetic inactivation studies have demonstrated that loss of SIN3B renders cells refractory to both replicative and oncogene-induced senescence, while its overexpression is sufficient to trigger senescence-associated heterochromatin formation. Furthermore, SIN3B interacts directly with key tumor suppressors such as p53 to mediate the repression of genes involved in cell cycle progression and with oncoproteins like Myc, promoting Myc deacetylation and degradation. In vivo, SIN3B has been shown to be required for KRAS- and PTEN-induced senescence in models of pancreatic and prostate cancer, respectively, underscoring its tumor-suppressive role under certain oncogenic conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in transcriptional repression and senescence, SIN3B contributes to the regulation of cell cycle control and cellular differentiation. By associating with the DREAM complex, SIN3B helps maintain quiescence through repression of a broad network of cell cycle‐related genes, while in vascular smooth muscle cells it is recruited—along with HDAC2 and the G9a methyltransferase—to mediate interferon-γ–induced repression of the collagen type I gene, linking inflammatory signals to chromatin modification. Moreover, functional studies in breast cancer models have revealed that SIN3B can promote invasive and metastatic behaviors, and recent genetic analyses have implicated SIN3B haploinsufficiency in a neurodevelopmental syndrome characterized by intellectual disability and autism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rakesh Singh Dhanda, Sofia Rondin Lindberg, Inge Olsson "}, {"type": "b", "children": [{"type": "t", "text": "The human SIN3B corepressor forms a nucleolar complex with leukemia-associated ETO homologues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Mol Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2199-9-8"}], "href": "https://doi.org/10.1186/1471-2199-9-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18205948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18205948"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "André Olsson, Inge Olsson, Rakesh Singh Dhanda "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional repression by leukaemia-associated ETO family members can be independent of oligomerization and coexpressed hSIN3B and N-CoR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagrm.2008.06.001"}], "href": "https://doi.org/10.1016/j.bbagrm.2008.06.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18586123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18586123"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Eduardo F Farias, Kevin Petrie, Boris Leibovitch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interference with Sin3 function induces epigenetic reprogramming and differentiation in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1006737107"}], "href": "https://doi.org/10.1073/pnas.1006737107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20547842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20547842"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Petar Jelinic, Jessica Pellegrino, Gregory David "}, {"type": "b", "children": [{"type": "t", "text": "A novel mammalian complex containing Sin3B mitigates histone acetylation and RNA polymerase II progression within transcribed loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00840-10"}], "href": "https://doi.org/10.1128/MCB.00840-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21041482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21041482"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tauheed Hasan, Mashook Ali, Daman Saluja, et al. "}, {"type": "b", "children": [{"type": "t", "text": "pH might play a role in regulating the function of paired amphipathic helices domains of human Sin3B by altering structure and thermodynamic stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (Mosc) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1134/S0006297915040057"}], "href": "https://doi.org/10.1134/S0006297915040057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25869359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25869359"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mark K Adams, Charles A S Banks, Janet L Thornton, et al. 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