Alternative titles; symbols
HGNC Approved Gene Symbol: SAFB2
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38) : 19:5,586,999-5,622,776 (from NCBI)
By sequencing cDNAs randomly selected from a cDNA library derived from the human immature myeloid cell line KG-1, Nagase et al. (1995) identified a partial cDNA, which they designated KIAA0138. Northern blot analysis detected expression in all human tissues and cell lines examined, with highest expression in kidney and lowest expression in liver.
By database searching with the sequence of nuclear matrix protein/scaffold attachment factor (SAFB; 602895) as query, Townson et al. (2003) identified KIAA0138, which they renamed SAFB2, as a member of the scaffold attachment factor family. SAFB2 encodes a deduced 953-amino acid protein with 75% homology to SAFB. Both SAFB and SAFB2 contain a highly conserved SAF box and RRM domain and both contain a nuclear localization signal. Using RT-PCR with SAFB2-specific primers, Townson et al. (2003) found that, like SAFB, SAFB2 is expressed in several breast cancer cell lines. Using SAFB- and SAFB2-specific probes in RNase protection assays, they found that the 2 genes are coexpressed in many tissues.
As had been shown for SAFB, Townson et al. (2003) found that SAFB2 functions as an estrogen receptor corepressor and that its overexpression results in inhibition of proliferation. SAFB and SAFB2 interact directly through a C-terminal domain, resulting in additive repression activity. Whereas SAFB is exclusively nuclear, SAFB2 is found in the cytoplasm as well as in the nucleus. Transfection experiments detected interaction between SAFB2 and vinexin, a protein involved in linking signaling to the cytoskeleton.
Using chromatin immunoprecipitation (ChIP)-on-chip and gene expression array analyses of MCF7 human breast cancer cells, Hammerich-Hille et al. (2010) identified 541 SAFB1- and/or SAFB2-binding sites in promoters of known genes. Enrichment of binding sites was observed in regions of chromosomes 1 and 6 containing histone gene clusters. Gene expression array analysis revealed upregulation of most target genes following knockdown of SAFB1 or SAFB2 via small interfering RNA. In general, SAFB2 regulated fewer genes than SAFB1, and there was relatively little overlap in the genes regulated by SAFB1 and SAFB2.
Using a FLASH RNA-protein interaction screen in HEK293 cells, Ilik et al. (2024) demonstrated that SAFB1, SAFB2, and SAFB-like transcriptional modulator (SLTM; 603421) bound to L1 RNA. By binding to L1 RNA, the SAFB proteins retained L1 RNA in the nucleus, thereby preventing L1 retrotransposition into new genetic loci. SAFB proteins also maintained splicing integrity by preventing exonization of previously integrated transposable elements (TEs). SAFB proteins could play this unique dual role because they bound to the conserved adenosine-rich coding sequences of L1. The suppressive activity of SAFB extended to tissue-specific, giant protein-coding cassette exons, nested genes, and Tigger DNA transposons. Moreover, SAFB also suppressed LTR/ERV elements in species in which they were still active, such as mice and flies. A significant subset of splicing events suppressed by SAFB in somatic cells was activated in testis, coinciding with low SAFB expression in postmeiotic spermatids. The authors concluded that SAFB proteins form an RNA-based, pattern-guided, nonadaptive defense system against TEs in the soma, complementing the RNA-based, adaptive Piwi-interacting RNA pathway (see 605571) of the germline.
Townson et al. (2003) determined that the SAFB and SAFB2 genes are adjacent and arranged in a head-to-head fashion, being separated by a short GC-rich intergenic region that can function as a bidirectional promoter. The bidirectional promoter contains a number of potential transcription factor binding sites, SP1 being the most frequent.
By sequence analysis, Townson et al. (2003) identified the SAFB2 gene adjacent to the SAFB gene on chromosome 19p13.3.
Hammerich-Hille, S., Kaipparettu, B. A., Tsimelzon, A., Creighton, C. J., Jiang, S., Polo, J. M., Melnick, A., Meyer, R., Oesterreich, S. SAFB1 mediates repression of immune regulators and apoptotic genes in breast cancer cells. J. Biol. Chem. 285: 3608-3616, 2010. [PubMed: 19901029] [Full Text: https://doi.org/10.1074/jbc.M109.066431]
Ilik, I. A., Glazar, P., Tse, K., Brandl, B., Meierhofer, D., Muller, F. J., Smith, Z. D., Aktas, T. Autonomous transposons tune their sequences to ensure somatic suppression. Nature 626: 1116-1124, 2024. [PubMed: 38355802] [Full Text: https://doi.org/10.1038/s41586-024-07081-0]
Nagase, T., Seki, N., Tanaka, A., Ishikawa, K., Nomura, N. Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 2: 167-174, 1995. [PubMed: 8590280] [Full Text: https://doi.org/10.1093/dnares/2.4.167]
Townson, S. M., Dobrzycka, K. M., Lee, A. V., Air, M., Deng, W., Kang, K., Jiang, S., Kioka, N., Michaelis, K., Oesterreich, S. SAFB2, a new scaffold attachment factor homolog and estrogen receptor corepressor. J. Biol. Chem. 278: 20059-20068, 2003. [PubMed: 12660241] [Full Text: https://doi.org/10.1074/jbc.M212988200]