Scaffold attachment
factor B (SAF-B)

Hsp27-estrogen response element (ERE)-TATA-binding protein (HET) (Oesterreich S. et al., 1997)
HnRNP A1 associated protein (HAP) (Weighardt F. et al., 1999)

Gene: maps to 19p13 (DuPont B.R. et al., 1997).
mRNA: size:
Protein: scaffold attachment factors are a subset of nuclear matrix proteins (NMP) that interact with matrix attachment regions. As predicted from the cDNA sequence, SAF-B contains 849 amino acids (96 696 Da), without significant homology to any known protein. SAF-B is rich in charged residues, leading to an aberrant migration on SDS gels, and has two putative bipartite nuclear localisation signals.
In heat shock protein 27 (HSP27), the majority of the promoter activity resides in the most proximal 200 bp. This region contains an imperfect estrogen response element (ERE) that is separated by a 13-bp spacer that contains a TATA box. Gel-shift analysis revealed the binding of a protein to this region that was neither the estrogen receptor nor TATA-binding protein. This new protein was termed Hsp27-ERE-TATA-binding protein (HET) and appeared identical to SAF-B. In transient transfection assays using hsp27 promoter-luciferase reporter constructs, HET overexpression resulted in a dose-dependent decrease of hsp27 promoter activity in several cell lines (Oesterreich S. et al., 1997).
Interphase chromatin is arranged into topologically separated domains comprising gene expression and replication units through genomic sequence elements, so-called MAR or SAR regions (for matrix- or scaffold-associating regions). S/MAR regions are located near the boundaries of actively transcribed genes and were shown to influence their activity. SAF-B, which specifically binds to S/MAR regions, was found to interact with RNA polymerase II (RNA pol II) and a subset of serine-/arginine-rich RNA processing factors (SR proteins). SAF-B localized to the nucleus in a speckled pattern that coincided with the distribution of the SR protein SC35. SAF-B could serve as a molecular base to assemble a 'transcriptosome complex' in the vicinity of actively transcribed genes (Nayler O. et al., 1998).

Cell lines:
- Cisplatin is an antitumor drug that is used to treat several types of cancers. The proteins that were cross-linked to DNA in situ in MCF-7 human breast cancer cells (BCC) incubated with cisplatin were analyzed. Cisplatin appeared to cross-link nuclear matrix proteins to DNA. In immunoblotting experiments, nuclear matrix-associated transcription factors and cofactors (estrogen receptor, HET/SAF-B, hnRNP K, and histone deacetylase 1) were found to be cross-linked to nuclear DNA (Samuel S.K. et al., 1998).

Tumors:

DuPont B.R. et al. (1997) Assignment of SAFB encoding Hsp27 ERE-TATA binding protein (HET)/scaffold attachment factor B (SAF-B) to human chromosome 19 band p13. Cytogenet. Cell Genet. 79, 284-285.
Nayler O. et al. (1998) SAF-B protein couples transcription and pre-mRNA splicing to SAR/MAR elements. Nucleic Acids Res. 26, 3542-3549.
Oesterreich S. et al. (1997) Novel nuclear matrix protein HET binds to and influences activity of the HSP27 promoter in human breast cancer cells. J. Cell Biochem. 67, 275-286.
Renz A. and Fackelmayer F.O. (1996) Purification and molecular cloning of the scaffold attachment factor B (SAF-B), a novel human nuclear protein that specifically binds to S/MAR-DNA. Nucleic Acids Res. 24, 843-849.
Samuel S.K. et al. (1998) In situ cross-linking by cisplatin of nuclear matrix-bound transcription factors to nuclear DNA of human breast cancer cells. Cancer Res. 58, 3004-3008.
Weighardt F. et al. (1999) A novel hnRNP protein (HAP/SAF-B) enters a subset of hnRNP complexes and relocates in nuclear granules in response to heat shock. J. Cell Sci. 112, 1465-1476.

Under construction