Functional relationship between transcription and the nuclear periphery: role of nuclear pores in transcription regulation?
A number of genes relocate to the nuclear periphery upon transcription activation. This association involves early transcription factors, as well elongation factors and mRNP components (Dieppois et al., 2006). Gene tethering to the nuclear periphery is proposed to positively influence transcription, but the molecular basis of this effect is poorly understood.
Our earlier work indicated that the nuclear pore associated Mlp1/2 proteins have been implicated in mRNA biogenesis and surveillance (Vinciguerra et al., 2005). These perinuclear proteins also anchor Ulp1, the major SUMO isopeptidase. Many nuclear proteins involved in DNA metabolism and transcription are modified by SUMO, but the exact role and regulation of this post-translational modification are still poorly defined.
Figure 2: Tup1 (and Ssn6?) transcription repressors are sumoylated, and their desumoylation by Ulp1 may promote fast relief of transcription repression and SAGA dependent activation at the NPC.
Recently, we observed that loss of Mlp proteins or delocalization of Ulp1 from the nuclear periphery result in increased transcription activation kinetics. Our current working model aims at testing whether the vicinity of the pore promotes transcription by facilitating desumoylation of DNA bound transcription repressors and activators by Ulp1 (Figure 2).