{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:44:50Z","timestamp":1760143490787,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:00:00Z","timestamp":1707782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical School, University of P\u00e9cs","award":["304566","K131588"],"award-info":[{"award-number":["304566","K131588"]}]},{"name":"National Research, Development and Innovation Fund, Hungary","award":["304566","K131588"],"award-info":[{"award-number":["304566","K131588"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>TEAD4 is a transcription factor that plays a crucial role in the Hippo pathway by regulating the expression of genes related to proliferation and apoptosis. It is also involved in the maintenance and differentiation of the trophectoderm during pre- and post-implantation embryonic development. An alternative promoter for the TEAD4 gene was identified through epigenetic profile analysis, and a new transcript from the intronic region of TEAD4 was discovered using the 5\u2019RACE method. The transcript of the novel promoter encodes a TEAD4 isoform (TEAD4-\u0394N) that lacks the DNA-binding domain but retains the C-terminal protein\u2013protein interaction domain. Gene expression studies, including end-point PCR and Western blotting, showed that full-length TEAD4 was present in all investigated tissues. However, TEAD4-\u0394N was only detectable in certain cell types. The TEAD4-\u0394N promoter is conserved throughout evolution and demonstrates transcriptional activity in transient-expression experiments. Our study reveals that TEAD4 interacts with the alternative promoter and increases the expression of the truncated isoform. DNA methylation plays a crucial function in the restricted expression of the TEAD4-\u0394N isoform in specific tissues, including the umbilical cord and the placenta. The data presented indicate that the DNA-methylation status of the TEAD4-\u0394N promoter plays a critical role in regulating organ size, cancer development, and placenta differentiation.<\/jats:p>","DOI":"10.3390\/ijms25042223","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T04:09:21Z","timestamp":1707797361000},"page":"2223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrative Epigenetic and Molecular Analysis Reveals a Novel Promoter for a New Isoform of the Transcription Factor TEAD4"],"prefix":"10.3390","volume":"25","author":[{"given":"Shima","family":"Rashidiani","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Medical Chemistry, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gizaw","family":"Mamo","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Medical Chemistry, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benj\u00e1min","family":"Farkas","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Medical Chemistry, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e1s","family":"Szabadi","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Medical Chemistry, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"},{"name":"Department of Dentistry, Oral and Maxillofacial Surgery, Medical School, University of P\u00e9cs, 7623 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1lint","family":"Farkas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"},{"name":"National Laboratory of Human Reproduction, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronika","family":"Uszkai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e1s","family":"Cs\u00e1sz\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Central Electron Microscope Laboratory, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e1lm\u00e1n","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"},{"name":"National Laboratory of Human Reproduction, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1220-8239","authenticated-orcid":false,"given":"Marianna","family":"Pap","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Central Electron Microscope Laboratory, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tibor A.","family":"Rauch","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Medical Chemistry, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0092-8674(03)00557-9","article-title":"The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis","volume":"114","author":"Harvey","year":"2003","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/gad.274027.115","article-title":"Mechanisms of Hippo pathway regulation","volume":"30","author":"Meng","year":"2016","journal-title":"Genes Dev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Snigdha, K., Gangwani, K.S., Lapalikar, G.V., Singh, A., and Kango-Singh, M. 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