Chromatin Remodeling by BRG1 and SNF2H : Biochemistry and Function

Chromatin is a highly dynamic, regulatory component in the process of transcription, repair, recombination and replication. The BRG1 and SNF2H proteins are ATP-dependent chromatin remodeling proteins that modulate chromatin structure to regulate DNA accessibility for DNA-binding proteins involved in these processes. The BRG1 protein is a central ATPase of the SWI/SNF complexes involved in chromatin remodeling associated with regulation of transcription. SWI/SNF complexes are biochemically hetero-geneous but little is known about the unique functional characteristics of the various forms. We have shown that SWI/SNF activity in SW13 cells affects actin filament organization dependent on the RhoA signaling pathway. We have further shown that the biochemical composition of SWI/SNF complexes qualitatively affects the remodeling activity and that the composition of biochemically purified SWI/SNF complexes does not reflect the patterns of chromatin binding of individual subunits. Chromatin binding assays (ChIP) reveal variations among subunits believed to be constitutive, suggesting that the plasticity in SWI/SNF complex composition is greater than suspected. We have also discovered an interaction between BRG1 and the splicing factor Prp8, linking SWI/SNF activity to mRNA processing. We propose a model whereby parts of the biochemical heterogeneity is a result of function and that the local chromatin environment to which the complex is recruited affect SWI/SNF composition. We have also isolated the novel B-WICH complex that contains WSTF, SNF2H, the splicing factor SAP155, the RNA helicase II/Guα, the transcription factor Myb-binding protein 1a, the transcription factor/DNA repair protein CSB and the RNA processing factor DEK. The formation of this complex is dependent on active transcription and links chromatin remodeling by SNF2H to RNA processing. By linking chromatin remodeling complexes with RNA processing proteins our work has begun to build a bridge between chromatin and RNA, suggesting that factors in chromatin associated assemblies translocate onto the growing nascent RNA.

E-Government Collaboration in the Swedish Public Sector : Multiple Studies on Collaboration Facilitators and Collaboration Modes

Collaboration in the public sector is imperative to achieve e-government objectives such as improved efficiency and effectiveness of public administration and improved quality of public services. Collaboration across organizational and institutional boundaries requires public organizations to share e-government systems and services through for instance, interoperable information technology and processes. Demands on public organizations to become more open also require that public organizations adopt new collaborative approaches for inviting and engaging citizens in governmental activities. E-government related collaboration in the public sector is challenging, however, and collaboration initiatives often fail. Public organizations need to learn how to collaborate since forms of e-government collaboration and expected outcomes are mostly unknown. How public organizations can collaborate and the expected outcomes are thus investigated in this thesis by studying multiple collaboration cases on the acquisition and implementation of a particular e-government investment (digital archive). This thesis also investigates how e-government collaboration can be facilitated through artifacts. It is done through a case study, where objects that cross boundaries between collaborating communities in the public sector are studied, and by designing a configurable process model integrating several processes for social services. By using design science, this thesis also investigates how an m-government solution that facilitates collaboration between citizens and public organizations can be designed. The thesis contributes to literature through describing five different modes of interorganizational collaboration in the public sector and the expected benefits from each mode. It also contributes with an instantiation of a configurable process model supporting three open social e-services and with evidence of how it can facilitate collaboration. This thesis further describes how boundary objects facilitate collaboration between different communities in an open government design initiative. It contributes with a designed mobile government solution, thereby providing proof of concept and initial design implications for enabling collaboration with citizens through citizen sourcing (outsourcing a governmental activity to citizens through an open call). This thesis also identifies research streams within e-government collaboration research through a literature review and the thesis contributions are related to the identified research streams. This thesis gives directions for future research by suggesting that future research should focus further on understanding e-government collaboration and how information and communication technology can facilitate collaboration in the public sector. It is suggested that further research should investigate m-government solutions to form design theories. Future research should also examine how value can be co-created in e-government collaboration.