자료유형  

 학위논문

Control Number  

0017160662

International Standard Book Number  

9798382835280

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Wong, Karen G.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pennsylvania., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

81 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.

General Note  

Advisor: Epstein, Jonathan A.

Dissertation Note  

Thesis (Ph.D.)--University of Pennsylvania, 2024.

Summary, Etc.  

요약Chromatin organization within the nucleus is not only important for normal cellular function but has also been demonstrated to play a role in the maintenance of cellular identity. Activation of the right genes at the right time is crucial for proper development, yet there is still much to uncover regarding how genes within repressed heterochromatin are accessed for transcription. The histone modification H3K9me2 is found on regions of chromatin that display a largely peripheral localization in the nucleus, an environment that is transcriptionally repressed. While it has been demonstrated that the movement of genomic loci from the nuclear periphery into the nuclear interior corresponds with activation of these regions, the molecular mechanisms that mediate detachment of chromatin from the lamina, increased accessibility to these regions, and transcriptional activation are unknown. Here, we utilize a growth factor signaling model to investigate how extracellular signals are transmitted through kinase cascades to influence epigenetic changes that modulate gene expression. We provide evidence that growth factor-stimulated upregulation in the transcript levels of many responsive genes is accompanied by increases in histone phosphorylation levels, specifically at H3K9me2S10 (histone H3 Serine 10 when the adjacent Lysine 9 is dimethylated). Imaging and proteomic approaches show that Epidermal Growth Factor (EGF) stimulation results in H3K9me2S10 phosphorylation, which occurs in genomic regions enriched for regulatory enhancers of EGF-responsive genes. We also demonstrate that the EGF-induced increase in H3K9me2S10ph is dependent on the nuclear kinase MSK2, and this subset of EGF-induced genes is dependent on MSK2 for transcription. Taken together, our work indicates that growth factor-induced changes in chromatin state can mediate the activation of downstream genes and has broader implications for understanding how lineage-specific genes and regulatory elements within H3K9me2-modified chromatin may be accessed during development.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Developmental biology.

Subject Added Entry-Topical Term  

Genetics.

Index Term-Uncontrolled  

Chromatin biology

Index Term-Uncontrolled  

Epigenetics

Index Term-Uncontrolled  

Growth factor signaling

Index Term-Uncontrolled  

MSK2

Index Term-Uncontrolled  

Phospho-methyl switch

Added Entry-Corporate Name  

University of Pennsylvania Cell and Molecular Biology

Host Item Entry  

Dissertations Abstracts International. 85-12B.

Electronic Location and Access  

로그인을 한후 보실 수 있는 자료입니다.

Control Number  

joongbu:658571