Nuclear organization by satellite DNA, SAF-A/hnRNPU and matrix attachment regions

The need of large-scale chromatin organization in the nucleus has become more and more appreciated. The higher order nuclear organization ultimately regulate a plethora of biological processes including transcription, DNA replication, and DNA repair. In this context, it is of critical importance to understand the mechanisms that allow higher order nuclear organization. Scaffold Attachment Factor A (SAF-A/hnRNPU), which was originally identified as the component of nuclear matrix, has emerged as an important regulator of higher order nuclear organization. It is shown that SAF-A/hnRNPU binds to tandem repeats (TRs) and scaffold/matrix attachment regions (S/MAR) in a sequence-non-specific, but structure-specific manner (e.g. DNA curvature). Recent studies showed that SAF-A interacts with chromatin-associated RNAs (caRNAs) to regulate interphase chromatin structures in a transcription-dependent manner. It is proposed that SAF-A/hnRNPU and caRNAs form a dynamic, transcriptionally responsive chromatin mesh that organizes chromatin in a large scale. The common structural features of S/MAR and pericentromeric (periCEN) TR promotes SAF-A-mediated association with each other. Collectively a model is presented wherein SAF-A/hnRNPU and periCEN TR are the key players in large-scale nuclear organization that supports general transcription.