EZH2 Regulates the Pre-antigen Receptor Checkpoint and B-2 Lineage Commitment /
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| Author / Creator: | Jacobsen, Jennifer Andrene, author. |
|---|---|
| Imprint: | 2017. Ann Arbor : ProQuest Dissertations & Theses, 2017 |
| Description: | 1 electronic resource (151 pages) |
| Language: | English |
| Format: | E-Resource Dissertations |
| Local Note: | School code: 0330 |
| URL for this record: | http://pi.lib.uchicago.edu/1001/cat/bib/11715110 |
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| 100 | 1 | |a Jacobsen, Jennifer Andrene, |e author. |0 (orcid)0000-0002-5354-6870 | |
| 245 | 1 | 0 | |a EZH2 Regulates the Pre-antigen Receptor Checkpoint and B-2 Lineage Commitment / |c Jennifer Andrene Jacobsen. |
| 260 | |c 2017. | ||
| 264 | 1 | |a Ann Arbor : |b ProQuest Dissertations & Theses, |c 2017 | |
| 300 | |a 1 electronic resource (151 pages) | ||
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| 500 | |a Advisors: Barbara L. Kee Committee members: Marcus R. Clark; Lucy A. Godley; Alexander Ruthenberg. | ||
| 502 | |b Ph.D. |c University of Chicago, Division of the Biological Sciences, Committee on Immunology; Pritzker School of Medicine |d 2017. | ||
| 506 | |a This item is not available from ProQuest Dissertations & Theses. | ||
| 510 | 4 | |a Dissertation Abstracts International, |c Volume: 78-12(E), Section: B. | |
| 520 | |a B lineage specification and commitment are carried out by transcription factors that activate the B lineage program and restrict alternate cell fates. How chromatin modifiers contribute to these two processes is not well understood. In this thesis I will examine the role of the histone methyltransferase EZH2 in early lymphocyte development and in B lineage specification and commitment. | ||
| 520 | |a EZH2 was previously reported to be required for B and T lymphopoiesis, but its role was not clear and it was unknown if it was required for innate lymphocyte development. I examined adaptive and innate lymphocyte development in Ezh2fl/fl Il7racre/+ mice and found that EZH2 was required in B and T cell progenitors to regulate the timing of the pre-antigen receptor checkpoint, but was dispensable for the development of innate lymphocytes. This study demonstrates a lineage specific role for EZH2 to regulate a common target gene, Cdkn2a, based on fundamental biological differences in the developmental requirements of innate and adaptive lymphocytes. | ||
| 520 | |a To understand the role of EZH2 in B lymphocyte specification and commitment, I promoted B progenitor survival by deleting the pre-antigen receptor checkpoint effector Cdkn2a. I found that EZH2-deficient pro-B cells maintained B lineage specification despite upregulation of innate lymphocyte genes in vitro and in vivo. Instead adult B-2 pro-B cells that lacked EZH2 converted to the fetal-associated B-1 lineage, concomitant with upregulation of the fetal RNA regulator Lin28b. These results indicate that EZH2 contributes to lineage commitment, but is not required to prevent conversion to non-B lineage fates. | ||
| 520 | |a In summary I have examined the role of EZH2 in early lymphocyte development and in B lineage specification and commitment. I have uncovered an essential mechanism by which EZH2 promotes B and T cell development, thereby offering an alternate explanation for the requirement of EZH2 during early B cell development, which was previously attributed to a role in antigen receptor recombination. I found that B lineage specification and commitment were differentially regulated by EZH2. This work allows us to redefine the requirements for lineage conversion based on the individual contributions of specification and commitment to the maintenance of B lineage identity. | ||
| 546 | |a English | ||
| 590 | |a School code: 0330 | ||
| 690 | |a Immunology. | ||
| 710 | 2 | |a University of Chicago. |e degree granting institution. |0 http://id.loc.gov/authorities/names/n79058404 |1 http://viaf.org/viaf/143657677 | |
| 720 | 1 | |a Barbara L. Kee |e degree supervisor. | |
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