MARC 主機 00000nam  2200373   4500 
001    AAI3445062 
005    20120912073710.5 
008    120912s2011    ||||||||||||||||| ||eng d 
020    9781124536330 
035    (UMI)AAI3445062 
040    UMI|cUMI 
100 1  Zullo, Joseph M 
245 10 DNA sequence and chromatin directed compartmentalization 
       of chromosomal domains to the nuclear lamina 
300    150 p 
500    Source: Dissertation Abstracts International, Volume: 72-
       06, Section: B, page: 3234 
500    Adviser: Harinder Singh 
502    Thesis (Ph.D.)--The University of Chicago, 2011 
520    Microscopy studies of metazoan cells have long suggested 
       that the nucleus is a highly structured organelle 
       consisting of multiple, distinct subcompartments and 
       proteinaceous structures. While correlative analyses have 
       generated many hypotheses to explain why such structures 
       may be important for various nuclear processes, efforts to
       validate these hypothesis functionally have been 
       frustrated by a lack of experimental models and tools. 
       Here, we develop such tools and assays in order to 
       elucidate the function of the nuclear lamina, a 
       compartment that has been suggested to play a role in 
       scaffolding transcriptionally inactive chromatin domains. 
       We demonstrate that the nuclear lamina harbors enzymatic 
       activities that function to both transcriptionally silence
       large sections of chromatin as well as physically tether 
       them to the inner nuclear membrane (INM). Furthermore, we 
       show that the mechanism by which this tethering occurs is 
       based on particular DNA-sequences, which we propose 
       recruit sequence specific transcription factors, histone 
       deacetylases and other chromatin modifying proteins to 
       create stable domains of epigenetic silencing at the 
       lamina. Additionally, we demonstrate that INM proteins 
       first make contact with these chromatin regions in late 
       anaphase, and suggest this interaction may aid in the 
       reassembly of the nuclear envelope following mitosis. 
       Finally, we identify a developmentally important 
       transcription factor, Ebf1, which is sufficient to 
       reposition a locus from the INM to the nuclear interior, 
       providing the first insight into how a specific lamina-
       associated region may be regulated during development. 
       Collectively, these studies represent the first rigorous 
       investigation into the processes that connect chromatin 
       organization and transcriptional regulation 
590    School code: 0330 
650  4 Biology, Molecular 
650  4 Biology, Cell 
690    0307 
690    0379 
710 2  The University of Chicago.|bMolecular Genetics and Cell 
773 0  |tDissertation Abstracts International|g72-06B 
856 40 |u