000231808 001__ 231808
000231808 005__ 20190619023719.0
000231808 0247_ $$2doi$$a10.5075/epfl-thesis-7797
000231808 02470 $$2urn$$aurn:nbn:ch:bel-epfl-thesis7797-4
000231808 02471 $$2nebis$$a11049845
000231808 037__ $$aTHESIS
000231808 041__ $$aeng
000231808 088__ $$a7797
000231808 245__ $$aGene regulatory dynamics underlying brown fat cell differentiation
000231808 269__ $$a2017
000231808 260__ $$bEPFL$$c2017$$aLausanne
000231808 300__ $$a136
000231808 336__ $$aTheses
000231808 502__ $$aProf. Matteo Dal Peraro (président) ; Prof. Bart Deplancke (directeur de thèse) ; Prof. Olaia Naveiras, Prof. Martin Klingenspor, Prof. Lluis Fajas (rapporteurs)
000231808 520__ $$aAdipose tissue is increasingly recognized as a dynamic, endocrine organ responsible for regulating metabolic homeostasis via the collective action of its two principal subtypes: white adipose tissue (WAT) and brown adipose tissue (BAT). Recently, the discovery of metabolically active brown fat reserves and brown in white fat (also known as "brite" or "beige" fat) in adult humans has prompted fundamental research to understand the development and function of brown adipocytes. The functional property of brown adipocytes is executed by the mitochondrial protein, Un- coupling Protein 1 (UCP1). UCP1 is responsible for uncoupling oxidative phosphorylation from ATP production thereby dissipating heat. The gene expression of Ucp1 is orchestrated by a multitude of transcriptional regulators and co-regulators that are distinct from those governing white adipocyte differentiation and function. However, in contrast to its counter- part, the white adipocyte, the gene regulatory mechanisms and transcriptional drivers of the brown adipocyte differentiation program remain elusive. Thus the focus of this thesis is to elucidate the gene regulatory network underlying brown fat cell differentiation and to decou- ple differentiation from the thermogenesis program using an integrative genomics approach. The main contributions of this work are as follows (1) construction of a comprehensive map integrating signaling, transcriptional and metabolic modules necessary for the activation of a brown adipocyte, (2) systematic, comprehensive analysis of transcriptional and chromatin state dynamics during brown fat cell differentiation leading to the identification of novel transcriptional regulators, (3) genomic characterization of the TF BCL6 during brown fat cell differentiation and (4) phenotypic characterization of a novel conditional BCL6 knockout mouse model.
000231808 6531_ $$abrown adipocyte
000231808 6531_ $$atranscriptomics
000231808 6531_ $$aepigenomics
000231808 6531_ $$acellular differentiation
000231808 6531_ $$agene regulation
000231808 6531_ $$asystems biology.
000231808 700__ $$0246853$$g220969$$aPradhan, Rachana Narendra
000231808 720_2 $$aDeplancke, Bart$$edir.$$g182376$$0244717
000231808 8564_ $$uhttps://infoscience.epfl.ch/record/231808/files/EPFL_TH7797.pdf$$zn/a$$s25965192$$yn/a
000231808 909C0 $$xU11829$$0252247$$pUPDEPLA
000231808 909CO $$pthesis-bn2018$$pthesis-public$$pDOI$$ooai:infoscience.tind.io:231808$$qGLOBAL_SET$$pSV$$pthesis$$qDOI2
000231808 917Z8 $$x108898
000231808 917Z8 $$x108898
000231808 918__ $$dEDBB$$cIBI-SV$$aSV
000231808 919__ $$aUPDEPLA
000231808 920__ $$b2017$$a2017-10-17
000231808 970__ $$a7797/THESES
000231808 973__ $$sPUBLISHED$$aEPFL
000231808 980__ $$aTHESIS