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Identification of HTRA4 as a Transcriptional Target of p63 in Trophoblast.
Donohoe, Mary E; Morey, Robert; Li, Yingchun; Pizzo, Donald; Kallol, Sampada; Cho, Hee-Young; Soncin, Francesca; Parast, Mana M.
Afiliación
  • Donohoe ME; Department of Pathology, University of California San Diego, La Jolla, California; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California.
  • Morey R; Department of Pathology, University of California San Diego, La Jolla, California; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California.
  • Li Y; Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado.
  • Pizzo D; Department of Pathology, University of California San Diego, La Jolla, California.
  • Kallol S; Department of Pathology, University of California San Diego, La Jolla, California; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California.
  • Cho HY; Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Soncin F; Department of Pathology, University of California San Diego, La Jolla, California; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California.
  • Parast MM; Department of Pathology, University of California San Diego, La Jolla, California; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California. Electronic address: mparast@health.ucsd.edu.
Am J Pathol ; 194(7): 1162-1170, 2024 07.
Article en En | MEDLINE | ID: mdl-38880601
ABSTRACT
The placenta plays a crucial role in pregnancy success. ΔNp63α (p63), a transcription factor from the TP53 family, is highly expressed in villous cytotrophoblasts (CTBs), the epithelial stem cells of the human placenta, and is involved in CTB maintenance and differentiation. We examined the mechanisms of action of p63 by identifying its downstream targets. Gene expression changes were evaluated following overexpression and knockdown of p63 in the JEG3 choriocarcinoma cell line, using microarray-based RNA profiling. High-temperature requirement A4 (HTRA4), a placenta-specific serine protease involved in trophoblast differentiation and altered in preeclampsia, was identified as a gene reciprocally regulated by p63, and its expression was characterized in primary human placental tissues by RNA-sequencing and in situ hybridization. Potential p63 DNA-binding motifs were identified in the HTRA4 promoter, and p63 occupancy at some of these sites was confirmed using chromatin immunoprecipitation, followed by quantitative PCR in both JEG3 and trophoblast stem cells. These data begin to identify members of the transcriptional network downstream of p63, thus laying the groundwork for probing mechanisms by which this important transcription factor regulates trophoblast stemness and differentiation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Trofoblastos Límite: Female / Humans / Pregnancy Idioma: En Revista: Am J Pathol Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Trofoblastos Límite: Female / Humans / Pregnancy Idioma: En Revista: Am J Pathol Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos