Repositorio UFRO · Omeka S

Multi-omics analyses demonstrate a critical role for EHMT1 methyltransferase in transcriptional repression during oogenesis

Primer Autor	Kelsey, Gavin
Co-autores	Demond, Hannah Hanna, Courtney W. Castillo-Fernandez, Juan Santos, Fatima Papachristou, Evangelia K. Segonds-Pichon, Anne Kishore, Kamal Andrews, Simon D'Santos, Clive S.
Título	Multi-omics analyses demonstrate a critical role for EHMT1 methyltransferase in transcriptional repression during oogenesis
Editorial	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Revista	GENOME RESEARCH
Lenguaje	en
Resumen	EHMT1 (also known as GLP) is a multifunctional protein, best known for its role as an H3K9me1 and H3K9me2 methyltransferase through its reportedly obligatory dimerization with EHMT2 (also known as G9A). Here, we investigated the role of EHMT1 in the oocyte in comparison to EHMT2 using oocyte-specific conditional knockout mouse models (Ehmt2 cKO, Ehmt1 cKO, Ehmt1/2 cDKO), with ablation from the early phase of oocyte growth. Loss of EHMT1 in Ehmt1 cKO and Ehmt1/2 cDKO oocytes recapitulated meiotic defects observed in the Ehmt2 cKO, however, there was a significant impairment in oocyte maturation and developmental competence in Ehmt1 cKO and Ehmt1/2 cDKO oocytes beyond that observed in the Ehmt2 cKO. Consequently, loss of EHMT1 in oogenesis results, upon fertilization, in mid-gestation embryonic lethality. To identify H3K9 methylation and other meaningful biological changes in each mutant to explore the molecular functions of EHMT1 and EHMT2, we performed immunofluorescence imaging, multi-omics sequencing, and mass spectrometry (MS)-based proteome analyses in cKO oocytes. Although H3K9me1 was depleted only upon loss of EHMT1, H3K9me2 was decreased, and H3K9me2-enriched domains were eliminated equally upon loss of EHMT1 or EHMT2. Furthermore, there were more significant changes in the transcriptome, DNA methylome, and proteome in Ehmt1/2 cDKO than Ehmt2 cKO oocytes, with transcriptional derepression leading to increased protein abundance and local changes in genic DNA methylation in Ehmt1/2 cDKO oocytes. Together, our findings suggest that EHMT1 contributes to local transcriptional repression in the oocyte, partially independent of EHMT2, and is critical for oogenesis and oocyte developmental competence.
Fecha Publicación	2023
Tipo de Recurso	artículo original
doi	10.1101/gr.277046.122
Formato Recurso	PDF
Palabras Claves	Animals Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism Mice Multiomics Oocytes / metabolism Oogenesis / genetics Proteome / metabolism
Ubicación del archivo	http://dx.doi.org/10.1101/gr.277046.122
Categoría OCDE	Bioquímica y biología molecular Biotecnología y microbiología aplicada Genética y herencia
Materias	Animales Histona-Lisina N-Metiltransferasa / genética Histona-Lisina N-Metiltransferasa/metabolismo Ratones multiómica Ovocitos/metabolismo Oogénesis/genética Proteoma / metabolismo
Identificador del recurso (Mandatado-único)	artículo original
Versión del recurso (Recomendado-único)	versión publicada
License	CC BY 4.0
Condición de la licencia (Recomendado-repetible)	CC BY 4.0
Derechos de acceso	acceso abierto
Access Rights	acceso abierto
Id de Web of Science	WOS:001052925400002
ISSN	1088-9051
Tipo de ruta	Verde# Hibrido
Categoría WOS	Bioquímica y biología molecular Biotecnología y microbiología aplicada Genética y herencia
Referencia del Financiador (Mandatado si es aplicable-repetible)	UK Biotechnology and Biological Sciences Research Council BBS/E/B/000C0423 Medical Research Council MR/K011332/1 Medical Research Council MR/S000437/1 ANID FONDECYT 3200676 CRUK A29580