Hypoxia-induced subnuclear re-distribution of SAFB1/2 alters their respective interactome

Oxygen deprivation (hypoxia) is encountered in physiological conditions but also characterizes many pathological conditions including ischemia and cancer. In order to survive, the cells usually rely upon the activation of the Hypoxia Inducible Factors (HIF), a small family of heterodimeric transcriptional activators. However, adaption to hypoxia also involves, lesser-known, HIF-independent processes that affect chromatin remodelling and nuclear architecture. SAFB1/2 (Scaffold Attachment Factors B1 and 2) are integral components of the nuclear matrix of vertebrate cells and known to affect functions that include transcriptional regulation, RNA processing and response to DNA damage. Our work indicates that SAFB1/2 swiftly change their localization from the insoluble matrix fraction to more soluble nuclear fractions in a HIF-independent manner. To extend our study, we performed immunoprecipitation experiments with SAFB1 or SAFB2 from cells exposed to both normoxia and short-term hypoxia (2 hours). Mass spectrometry analysis of the immunoprecipitates revealed that short-term exposure of cells to low oxygen levels alters the protein-protein interactions of SAFB1/2 mainly with proteins implicated in mRNA maturation and transcriptional control. Our data suggest that SAFB1/2 proteins participate in molecular mechanisms immediately responsive to hypoxia that entail their rapid mobilization from the nuclear matrix and their altered association with constituents of splicing and transcriptional machinery.