자료유형  

 학위논문

Control Number  

0017160281

International Standard Book Number  

9798381972078

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

McIntyre, Tara.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of California, San Francisco., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

247 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-09, Section: B.

General Note  

Advisor: Fisher, Susan.

Dissertation Note  

Thesis (Ph.D.)--University of California, San Francisco, 2024.

Summary, Etc.  

요약Timing mechanisms in biology remain poorly understood. As one prime example, little is known about the mechanisms that specify how long the gestating uterus will remain quiescent before entering labor. Our lack of insight into this fundamental question, which applies to all mammalian species, also limits investigation into potential causes of preterm labor, a major human pregnancy complication. My dissertation work provides evidence that gestation length in mice is determined by an epigenetic timer that runs autonomously within the fibroblasts of the pregnant uterus. The timer is set during the peri-implantation period when select loci establish appropriate levels of the repressive histone mark H3K27me3. These loci then progressively lose H3K27me3, thereby scheduling the uterine cell state transitions and associated gene expression changes of late gestation that are the proximal mediators of luteolysis (progesterone withdrawal) and labor onset. Initial overwinding of the timer via genetic ablation of the histone demethylase KDM6B delays these transitions and extends gestation length. My findings also demonstrate requirements for KDM6 demethylases in inflammation-induced preterm labor, and suggest potential requirements for KDM6B in the uterine-intrinsic pathways of parturition that are distinct from luteolysis. These results unexpectedly implicate epigenetic pathways in fibroblasts as a top-level determinant of both normal and pathological parturition mechanisms. We anticipate that further dissection of the ways such fibroblast programming controls gestation length may suggest novel approaches for improving human pregnancy outcomes.

Subject Added Entry-Topical Term  

Biology.

Index Term-Uncontrolled  

epigenetics

Index Term-Uncontrolled  

fibroblasts

Index Term-Uncontrolled  

H3K27me3

Index Term-Uncontrolled  

parturition

Index Term-Uncontrolled  

pregnancy

Index Term-Uncontrolled  

uterus

Added Entry-Corporate Name  

University of California, San Francisco Biomedical Sciences

Host Item Entry  

Dissertations Abstracts International. 85-09B.

Electronic Location and Access  

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Control Number  

joongbu:654626