PhD Scientific Days 2024

Poster Session K - Theoretical and Translational Medicine 2.

Links between the evolution of the zinc finger 554 (ZNF554) gene in anthropoid primates, deep placentation, and its impairment in preeclampsia

Előadó neve

Dr. Posta, Máté

Neptun code

DP77CG

Előadó munkahelye

Systems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary

Előadó telefonszáma

06209925764

Előadó e-mail címe

posta.mate@gmail.com

Az előadás címe

Links between the evolution of the zinc finger 554 (ZNF554) gene in anthropoid primates, deep placentation, and its impairment in preeclampsia

Szerző(k) neve és munkahelye

Máté Posta¹, Orsolya Oravecz², Roberto Romero³, Yi Xu⁴, Kata Juhász⁵, Andrea Balogh⁵, Emese Farkas¹, Zhonghui Xu⁴, Zsolt Gelencsér⁵, Gábor Szalai⁵, Petronella Hupuczi⁶, Padma Murthi⁷, Martin Knöfler⁸, Offer Erez⁹, Adi L. Tarca¹⁰, Nándor Ács¹¹, Zoltán Papp¹², Nándor Gábor Than¹³

1: Systems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary; Doctoral College, Károly Rácz Conservative Medicine Division, Semmelweis University, Budapest, Hungary
2: Systems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary;; Doctoral School of Biology, Institute of Biology, ELTE Eötvös Loránd University, Budapest, Hungary
3: Perinatology/Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, United States
4: Perinatology/Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States
5: Systems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary;
6: Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary
7: Department of Pharmacology, Monash Biomedicine Discovery Institute, Clayton, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, Parkville, Australia;
8: Placental Development Group, Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria;
9: Perinatology/Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, United States; Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel;
10: Perinatology/Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, United States;
11: Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary;
12: Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary; Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary;
13: Systems Biology of Reproduction Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary; Perinatology/Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, United States; Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary; Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary;

Bemutatás módja

Poszter

Szekció

Poster Session K - Theoretical and Translational Medicine 2.

Language of the presentation

Hungarian

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Earlier we demonstrated that ZNF554 is a transcription factor highly expressed in the placenta and regulates trophoblastic functions, including migration and invasion, and its expression is severely downregulated via promoter hypermethylation in preeclampsia. Here, we investigated how the evolution of the ZNF554 locus affected the regulation of placental ZNF554 expression, trophoblast invasion, and the vulnerability to preeclampsia.
The evolution of the ZNF554 locus was examined in silico. The transcriptional regulation of ZNF554 by ZEB1, ZEB2, and hypoxia via transcription factors sites in the 5' flanking region was in vitro investigated by luciferase assays. We also studied hypoxia-response elements (HREs) located in the 5' flanking region and their hypermethylation in preeclampsia. In addition, we analyzed the functional relevance of these HREs by luciferase assays.
The evolution of the ZNF554 locus in primates involved the insertion of primate-specific transposable elements (AluY and LTR10A) into the 5' flanking region, which established ZEB binding sites and HREs. In humans, a 29bp fragment of the LTR10A was adjacently multiplicated 34 times, which introduced 34 ZEB binding sites into the ZNF554 locus. Co-transfection with ZEB1/2 led to increased reporter activity in extravillous trophoblasts, which was affected by oxygen concentration, showing the importance of the ZEB-ZNF554 axis in the regulation of trophoblast migration and invasion. The deletion of CpGs in HREs in AluY decreased reporter activity, functionally validating our clinical data on that decreased ZNF554 expression in preterm preeclampsia is epigenetically regulated.
Our study revealed that evolutionary changes in the ZNF554 locus enabled the regulation of ZNF554 expression by hypoxia and ZEB transcription factors in extravillous trophoblasts, facilitating deep trophoblast invasion in humans. Our data suggest that ZNF554 downregulation by epigenetic mechanisms is involved in preeclampsia pathology.
This research was funded by the MTA (LP2014-7/2014, Premium_2019-436) and by NKFIH (OTKA K128262, 2019-2.1.7-ERA-NET-2020-00014) grants. Supported by the ÚNKP-23-3 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund (ÚNKP-23-3-II-ELTE-174).

University

Semmelweis University

Supervisor

Nándor Gábor Than

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8069

Start

16:15

End

16:18