Actions for Transcriptional Regulation Of Erythropoiesis Via High Resolution Chip-exo

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Transcriptional Regulation Of Erythropoiesis Via High Resolution Chip-exo

Author
Han, Garam
Published
[University Park, Pennsylvania] : Pennsylvania State University, 2015.
Physical Description
1 electronic document
Additional Creators
Pugh, B. Franklin
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Open Access.
Summary
Regulation of gene expression is important for cell differentiation and growth in eukaryotic cells. Precise and complex temporal and spatial regulation enables cells to express various transcriptomes, thus function differently despite having identical genomes. Numerous proteins interact with DNA in the genome or other proteins to regulate this process. Thus, determining the precise locations of protein-DNA interaction is important to understand how they regulate gene expression. Erythropoiesis, differentiation of multiprogenitor cells to red blood cells, serves as an excellent system to study the process to cellular differentiation, which requires precise and intricate transcriptional regulation. GATA1 and TAL1 are two key erythroid transcription factors (TFs) that form a multicomponent complex to regulate this process. However, the precise positional organization of these TFs in the genome remains unclear. Here we applied high resolution ChIP-exo to GATA1 and TAL1 to study their positional organization and determinants of their binding during GATA1-dependent development in mouse. Two complementary methods, MultiGPS and peak pairing, were implemented to determine confident binding locations. While ChIP-exo and ChIP-seq showed substantial overlap in their binding locations, high resolution of binding reveals the homotypic clusters of GATA1 and TAL1 binding locations and the precise positional organization within the protein complex, which cannot be detected using ChIP-seq. We show that the presence of TG (half E-box) 7~8 bp upstream of WGATAA is a strong determinant for co-occupancy of GATA1 and TAL1. Furthermore, we confirm differential GATA1 binding along the time points of erythroid differentiation. This differential recruitment of GATA1 influences gene expression positively when these binding events are nearer to the transcription start sites.
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Dissertation Note
Ph.D. Pennsylvania State University, 2015.
Reproduction Note
Microfilm (positive). 1 reel ; 35 mm. (University Microfilms 10-609575)
Technical Details
The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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