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Vetrivel, S.* ; Truong, D.-J.J. ; Wurst, W. ; Graw, J. ; Giesert, F.

Identification of ocular regulatory functions of core histone variant H3.2.

Exp. Eye Res. 226:109346 (2023)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The posttranscriptional modifications (PTM) of the Histone H3 family play an important role in ocular system differentiation. However, there has been no study on the nature of specific Histone H3 subtype carrying these modifications. Fortuitously, we had previously identified a dominant small-eye mutant Aey69 mouse with a mutation in the H3.2 encoding Hist2h3c1 gene (Vetrivel et al., 2019). In continuation, in the present study, the role of Histone H3.2 with relation to the microphtalmic Aey69 has been elaborated. Foremost, a transgenic mouse line expressing the fusion protein H3.2-GFP was generated using Crispr/Cas9. The approach was intended to confer a unique tag to the Hist2h3c1 gene which is similar in sequence and encoded protein structure to other histones. The GFP tag was then used for ChIP Seq analysis of the genes regulated by H3.2. The approach revealed ocular specific H3.2 targets including Ephrin family genes. Altered enrichment of H3.2 was found in the mutant Aey69 mouse, specifically around the ligand Efna5 and the receptor Ephb2. The effect of this altered enrichment on Ephrin signaling was further analyzed by QPCR and immunohistochemistry. This study identifies Hist2h3c1 encoded H3.2 as an important epigenetic player in ocular development. By binding to specific regions of ocular developmental factors Histone H3.2 facilitates the function of these genes for successful early ocular development.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chip Seq ; Ephrins ; Eye Development ; Histone H3.2; Gene-expression; Mouse; Eye; Integrity; Model; Pax6; Mice
Sprache englisch
Veröffentlichungsjahr 2023
Prepublished im Jahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 0014-4835
e-ISSN 1096-0007
Zeitschrift Experimental Eye Research
Quellenangaben Band: 226, Heft: , Seiten: , Artikelnummer: 109346 Supplement: ,
Verlag Elsevier
Verlagsort 24-28 Oval Rd, London Nw1 7dx, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Insitute of Synthetic Biomedicine (ISBM)
POF Topic(s) 30204 - Cell Programming and Repair
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-500500-001
G-500500-002
G-509300-001
Förderungen Helmholtz Alliance 'Aging and Metabolic Programming, AMPro'
Helmholtz Portfolio Theme 'Metabolic Dysfunction and Common Disease'
German Academic Exchange Service (DAAD)
DOI 10.1016/j.exer.2022.109346
WOS ID 000912488500001
WOS ID WOS:000912488500001
Scopus ID 85144313948
PubMed ID 36529279
Erfassungsdatum 2022-12-20
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