Disease relevance of BANF1

• BAF has roles in nuclear assembly, chromatin organization, gene expression, and gonad development and is exploited by retroviruses [1].
• Mutants that bound DNA efficiently reconstituted HIV-1 integration, even though in one case binding was just 0.2% of wild-type BAF [2].
• Both the structure and DNA binding function of the barrier-to-autointegration factor contribute to reconstitution of HIV type 1 integration in vitro [2].
• Thus, Ser-4-unphosphorylated BAF has a positive role in localizing emerin; this role may be disease relevant because loss or mislocalization of emerin causes Emery-Dreifuss muscular dystrophy [3].
• We conclude that BAF is present at low levels in incoming virions, in addition to being acquired from the cytoplasm of newly infected cells [4].

High impact information on BANF1

• Recently, beta-actin was found to be a component of mammalian SWI/SNF-like BAF chromatin remodeling complexes and still more recently other SWI/SNF-related chromatin remodeling complexes in yeast, flies, and man [5].
• The mammalian BAF complex regulates gene expression by modifying chromatin structure [6].
• BAF is also a host cell component of retroviral pre-integration complexes [7].
• We used site-directed mutagenesis and biochemical analysis to map functionally important residues in human BAF, including those required for direct binding to DNA or emerin [8].
• Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA [9].

Biological context of BANF1

• An in vitro binding assay involving an emerin S175A point mutant protein suggested that phosphorylation at Ser175 regulates the dissociation of emerin from BAF [10].
• Barrier-to-autointegration factor (BAF), a protein that binds nonspecifically to double-stranded DNA in vitro, co-localized with emerin at the 'core' region of chromosomes during telophase [11].
• In HeLa cells that expressed BAF mutant G25E, which did not show 'core' localization, the endogenous emerin proteins failed to localize at the 'core' region during telophase, and did not assemble into the NE during the subsequent interphase [11].
• Thus, BAF is dynamic and mobile during interphase, in stark contrast to its nuclear envelope partners [12].
• Fluorescence resonance energy transfer (FRET) results showed that CFP-BAF binds directly to YFP-emerin at the inner nuclear membrane of living cells [12].

Anatomical context of BANF1

• Overexpression studies in HeLa cells show that BAF-L, like BAF, is a predominantly nuclear protein [1].
• Dissociation of emerin from barrier-to-autointegration factor is regulated through mitotic phosphorylation of emerin in a xenopus egg cell-free system [10].
• BAF is required for emerin assembly into the reforming nuclear envelope [11].
• It is believed that emerin is part of a novel nuclear protein complex consisting of the barrier-to-autointegration factor (BAF), the nuclear lamina, nuclear actin and other associated proteins [13].
• However, we identified two human tissues (of 16 tested) in which BAF mRNA was not detected: thymus and peripheral blood leukocytes, which are enriched in CD4(+) T lymphocytes and macrophage precursors, respectively [4].

Associations of BANF1 with chemical compounds

• The functional importance of MRP4 and BCRP in the urinary excretion of HCT and furosemide was investigated using gene knockout mice [14].
• A G-CSF-R mutant was constructed in which tryptophan 650 was replaced by arginine and expressed in BAF3 cells (BAF/W650R) [15].
• The breast cancer resistance protein (BCRP) is an ATP-binding cassette half transporter that confers resistance to anticancer drugs such as mitoxantrone, anthracyclines, topotecan, and SN-38 [16].
• The V-ICEinh and BAF, two peptide inhibitors of cysteine aspartases, protected neurons in all three death paradigms [17].
• A disparity was noted in the transport of rhodamine 123 among nine MXR/BCRP/ABCP-overexpressing cells studied; all demonstrated mitoxantrone transport, whereas only two effluxed rhodamine 123 [18].

Physical interactions of BANF1

• An emerin mutant defective for binding to BAF in vitro failed to localize at the 'core' in vivo, and subsequently failed to localize at the reformed NE [11].
• We report that BAF binds directly and selectively to linker histone H1.1 (among three subtypes tested) and core histone H3 with affinities of approximately 700 nm and approximately 100-200 nm, respectively, in vitro and in vivo [19].

Other interactions of BANF1

• Sequence alignments identified a potential BAF-binding motif, characterized by the conserved residues Ser-Arg-Val, in MAN1-C and two other BAF-binding proteins [20].
• Binding of barrier to autointegration factor (BAF) to histone H3 and selected linker histones including H1.1 [19].
• Mutations at the bottom and top surfaces of the BAF dimer disrupted or enhanced, respectively, this binding and affected H1 and H3 similarly [19].
• LAP2beta is a type II integral protein of the inner nuclear membrane, which binds to lamin B and the chromosomal protein BAF, and may link the nuclear membrane to the underlying lamina and provide docking sites for chromatin [21].
• Emerin and lamin A together form stable complexes with either BAF or GCL in vitro [22].

Analytical, diagnostic and therapeutic context of BANF1

• Mu-mediated PCR footprinting revealed that of these three purified proteins, only BAF restored the native structure of the HIV-1 protein-DNA intasome [23].
• An improved specimen table for the Balzers freeze etching system BAF 400 [24].
• We studied the specificity and sensitivity of the four signs related with the accommodative insufficiency: high MEM dynamic retinoscopy, failing MAF and BAF with minus lenses of +/- 2 D flipper lenses, and low PRA [25].
• Baf60c overexpressed in cell culture can mediate interactions between cardiac transcription factors and the BAF complex ATPase Brg1, thereby potentiating the activation of target genes [26].
• ABCG2 is likely to limit the bioavailability of JNJ-7706621 because oral administration of JNJ-7706621 to Bcrp (the murine homologue of ABCG2) knockout mice resulted in an increase in the plasma concentration of JNJ-7706621 compared with wild-type mice [27].

References