Objective This proposed study addresses a major issue in the field of genome biology: how cells adopt specific genome configuration during differentiation, how is it maintained, and how properties of nuclear architecture relate to cell function.Although spatial clustering of genes and regulatory elements is correlated with transcription status and epigenetic states, it is not clear which mechanisms drive, which features follow, and what is the regulatory role of nuclear organization.Our studies in numerous cell types have identified the enrichment for transcription factor (TF) binding loci as the salient feature of genomic loci residing in active sub-nuclear environments. Surprisingly, the coordinated chromosomal associations were not correlated with transcription response. Thus, we hypothesize that TF interactions with the genome are key for the establishment of genome three-dimensional organization.To understand how nuclear architecture is modulated during differentiation we propose to study the coupled dynamics of genomic association networks together with multiple genomic layers of genome regulation (transcription, transcription factor binding, and epigenetic states) during adipogenic differentiation in high temporal resolution. Moreover, genome architecture data will be combined with DHS-seq profiles for unbiased examinations and discovery of nuclear organizing factors. To understand how genome organization is maintained we will study differentiated mammary cells. We will validate our findings with molecular perturbations, and combine genomics with single cell analysis by imaging. Lastly, to understand genome organization transitions, we will study the dynamics of genome organization throughout the cell cycle in high molecular and temporal resolutions. Importantly, we will link nuclear organization to cellular function by studying functional and terminal differentiation. Fields of science natural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2013-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator BAR ILAN UNIVERSITY Address Bar ilan university campus 52900 Ramat gan Israel See on map Activity type Higher or Secondary Education Establishments Administrative Contact Estelle Waise (Ms.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
