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Integration of the Heat Shock Pathway With a Master Transcriptional Regulator Drives Temperature-Dependent Morphogenesis in Histoplasma
Integration of the Heat Shock Pathway With a Master Transcriptional Regulator Drives Temperature-Dependent Morphogenesis in Histoplasma
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103206
- ISBN
- 9798280748590
- DDC
- 574
- 서명/저자
- Integration of the Heat Shock Pathway With a Master Transcriptional Regulator Drives Temperature-Dependent Morphogenesis in Histoplasma
- 발행사항
- [Sl] : University of California, San Francisco, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 116 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Sil, Anita;Mukherjee, Shaeri.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2025.
- 초록/해제
- 요약The ability of microbes to sense and respond to various environmental signals is critical for their survival in different niches. Thermally dimorphic fungal pathogens, including Histoplasma, undergo dramatic changes in cell morphology and gene expression in response to temperature. How these fungi sense temperature and switch their developmental forms in response is a long-standing mystery. In the environment, Histoplasma grows as a multicellular hyphal form that produces vegetative spores. Upon inhalation by a mammalian host, spores undergo a developmental change to a parasitic yeast form that secretes virulence factors and causes disease. Here, we report dynamic changes in the Histoplasma transcriptome across yeast-to-hypha transition. Expression of the vast majority of these transcripts is dependent upon the Ryp transcription factors, which were previously identified in our laboratory to be key regulators of the morphogenesis program in Histoplasma. Using genome-wide chromatin immunoprecipitation studies, we provide evidence that Ryp1, Ryp2, and Ryp3 rapidly dissociate from DNA in a temperature-dependent manner, and that this dissociation accounts for downstream transcriptomic changes in known morphological regulators. We additionally identify a role for Ryp2 alongside Hsf1, the conserved transcriptional regulator of the heat shock pathway in eukaryotes, in the direct regulation of heat shock genes such as HSP90 and HSP70. Finally, we uncover that the heat shock pathway is required for yeast-phase growth. This study highlights for the first time a link between the heat shock pathway, which is intrinsically temperature-sensitive, and the Ryp transcription factors, which control morphology in Histoplasma, providing insight into how Histoplasma and other thermal dimorphs sense temperature and relay this signal into downstream pathways involved in morphogenesis and virulence.
- 일반주제명
- Molecular biology
- 일반주제명
- Biochemistry
- 일반주제명
- Microbiology
- 일반주제명
- Pathology
- 키워드
- Gene regulation
- 키워드
- Morphogenesis
- 기타저자
- University of California, San Francisco Biochemistry and Molecular Biology
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798280748590
■035 ▼a(MiAaPQ)AAI32000053
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aMorrison, Anna Christine.▼0(orcid)0000-0002-5806-9831
■24510▼aIntegration of the Heat Shock Pathway With a Master Transcriptional Regulator Drives Temperature-Dependent Morphogenesis in Histoplasma
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a116 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Sil, Anita;Mukherjee, Shaeri.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2025.
■520 ▼aThe ability of microbes to sense and respond to various environmental signals is critical for their survival in different niches. Thermally dimorphic fungal pathogens, including Histoplasma, undergo dramatic changes in cell morphology and gene expression in response to temperature. How these fungi sense temperature and switch their developmental forms in response is a long-standing mystery. In the environment, Histoplasma grows as a multicellular hyphal form that produces vegetative spores. Upon inhalation by a mammalian host, spores undergo a developmental change to a parasitic yeast form that secretes virulence factors and causes disease. Here, we report dynamic changes in the Histoplasma transcriptome across yeast-to-hypha transition. Expression of the vast majority of these transcripts is dependent upon the Ryp transcription factors, which were previously identified in our laboratory to be key regulators of the morphogenesis program in Histoplasma. Using genome-wide chromatin immunoprecipitation studies, we provide evidence that Ryp1, Ryp2, and Ryp3 rapidly dissociate from DNA in a temperature-dependent manner, and that this dissociation accounts for downstream transcriptomic changes in known morphological regulators. We additionally identify a role for Ryp2 alongside Hsf1, the conserved transcriptional regulator of the heat shock pathway in eukaryotes, in the direct regulation of heat shock genes such as HSP90 and HSP70. Finally, we uncover that the heat shock pathway is required for yeast-phase growth. This study highlights for the first time a link between the heat shock pathway, which is intrinsically temperature-sensitive, and the Ryp transcription factors, which control morphology in Histoplasma, providing insight into how Histoplasma and other thermal dimorphs sense temperature and relay this signal into downstream pathways involved in morphogenesis and virulence.
■590 ▼aSchool code: 0034.
■650 4▼aMolecular biology
■650 4▼aBiochemistry
■650 4▼aMicrobiology
■650 4▼aPathology
■653 ▼aFungal pathogenesis
■653 ▼aGene regulation
■653 ▼aMorphogenesis
■653 ▼aTemperature-sensing
■653 ▼aTranscription factor
■690 ▼a0307
■690 ▼a0487
■690 ▼a0410
■690 ▼a0571
■71020▼aUniversity of California, San Francisco▼bBiochemistry and Molecular Biology.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357317▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
