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Full-Text Articles in Molecular Biology

Function Of Bromodomain And Extra-Terminal Motif Proteins (Bets) In Gata1-Mediated Transcription, Aaron James Stonestrom Jan 2015

Function Of Bromodomain And Extra-Terminal Motif Proteins (Bets) In Gata1-Mediated Transcription, Aaron James Stonestrom

Publicly Accessible Penn Dissertations

Bromodomain and Extra-Terminal motif proteins (BETs) associate with acetylated histones and transcription factors. While pharmacologic inhibition of this ubiquitous protein family is an emerging therapeutic approach for neoplastic and inflammatory disease, the mechanisms through which BETs act remain largely uncharacterized. Here we explore the role of BETs in the physiologically relevant context of erythropoiesis driven by the transcription factor GATA1. First, we characterize functions of the BET family as a whole using a pharmacologic approach. We find that BETs are broadly required for GATA1-mediated transcriptional activation, but that repression is largely BET-independent. BETs support activation by facilitating both GATA1 occupancy ...


Deciphering Arap3 Functions In Hematopoiesis And Hematopoietic Stem Cells, Yiwen Song Jan 2015

Deciphering Arap3 Functions In Hematopoiesis And Hematopoietic Stem Cells, Yiwen Song

Publicly Accessible Penn Dissertations

ARAP3 is a GTPase-activating protein that inactivates Arf6 and RhoA GTPases. ARAP3 deficiency in mice causes a sprouting angiogenic defect resulting in embryonic lethality by E11. Mice with an ARAP3 R302,303A mutation (KI/KI) that prevents activation by PI3K have a similar angiogenic phenotype, although rare animals survive to adulthood. Although ARAP3 was first discovered in porcine leukocytes, it remains largely unstudied in hematopoiesis and hematopoietic stem cells (HSCs). In this thesis, we aim to elucidate the potential cell-autonomous and non-cell-autonomous roles of ARAP3 in hematopoiesis and HSCs using several conditional knockout (CKO) transgenic mouse models in addition to ...


Higher-Order Chromatin Organization In Hematopoietic Transcription, Wulan Deng Jan 2012

Higher-Order Chromatin Organization In Hematopoietic Transcription, Wulan Deng

Publicly Accessible Penn Dissertations

Coordinated transcriptional networks underlie complex developmental processes. Transcription factors play central roles in such networks by binding to core promoters and regulatory elements and thereby controlling transcription activities and chromatin states in the genome. GATA1 is a hematopoietic transcription factor that controls multiple hematopoietic lineages by activating and repressing gene expression, yet the in vivo mechanisms that specify these opposing activities are unknown. By examining the composition of GATA1 associated protein complexes in a genetic complementary erythroid cell system as well as through the use of tiling arrays, we found that a multi-protein complex containing SCL/TAL1, LMO2, Ldb1, and ...