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Hdac3 ensures stepwise epidermal stratification via ncor/smrt-reliant mechanisms independent of its histone deacetylase activity / Katherine Margaret Szigety.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Szigety, Katherine Margaret, author.
- Language:
- English
- Subjects (All):
- Developmental biology.
- Biochemistry and Molecular Biophysics--Penn dissertations.
- Penn dissertations--Biochemistry and Molecular Biophysics.
- Local Subjects:
- Developmental biology.
- Biochemistry and Molecular Biophysics--Penn dissertations.
- Penn dissertations--Biochemistry and Molecular Biophysics.
- Genre:
- Academic theses.
- Physical Description:
- 1 online resource (89 pages)
- Contained In:
- Dissertations Abstracts International 81-10B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2020.
- Language Note:
- English
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- Chromatin modifiers play critical roles in epidermal development, but the functions of histone deacetylases in this context are poorly understood. We find that the class I HDAC, HDAC3, is expressed broadly in embryonic epidermis. To delineate its roles in epidermal development, we have employed loss of function genetic analyses in mice. We show that HDAC3 is required for its orderly stepwise stratification. Stability of HDAC3 protein in vivo is reliant on NCoR and SMRT, which function redundantly in epidermal development. However, point mutations in the NCoR and SMRT Deacetylase Activating Domains, which are required for HDAC3's enzymatic function, permit normal stratification, indicating that HDAC3's roles in this context are independent of its histone deacetylase activity. HDAC3 functions both in conjunction with, and independent of, KLF4 to repress premature expression of different sets of terminal differentiation genes and suppresses expression of inflammatory cytokines through a RelA-dependent mechanism. These data identify HDAC3 as a hub coordinating multiple aspects of epidermal barrier acquisition.
- Notes:
- Source: Dissertations Abstracts International, Volume: 81-10, Section: B.
- Advisors: Millar, Sarah E.; Committee members: Kristen Lynch; Mitchell Lazar; George Cotsarelis; Edward Morrisey; Elizabeth Grice; Brian Capell.
- Department: Biochemistry and Molecular Biophysics.
- Ph.D. University of Pennsylvania 2020.
- Local Notes:
- School code: 0175
- ISBN:
- 9798607313029
- Access Restriction:
- Restricted for use by site license.
- This item is not available from ProQuest Dissertations & Theses.
- This item must not be sold to any third party vendors.
- This item must not be added to any third party search indexes.
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