Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing

Autor: Akihiko Okuda, Ayumu Suzuki, Kentaro Mochizuki, Kenjiro Shirane, Haruhiko Koseki, Kousuke Uranishi, Aaron B. Bogutz, Jafar Sharif, Matthew C. Lorincz, Sanne M. Janssen
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Epigenomics
Male
Methyltransferase
General Physics and Astronomy
E2F6 Transcription Factor
Polycomb-Group Proteins
Germline
Epigenesis
Genetic
Histones
Mice
0302 clinical medicine
Genes
Reporter
Basic Helix-Loop-Helix Transcription Factors
Polycomb Repressive Complex 1
0303 health sciences
Multidisciplinary
biology
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Gene Expression Regulation
Developmental
Mouse Embryonic Stem Cells
Cell biology
Histone
DNA methylation
Female
Signal Transduction
Ubiquitin-Protein Ligases
Science
Green Fluorescent Proteins
Mice
Transgenic
macromolecular substances
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Gene silencing
Animals
Embryo Implantation
Gene Silencing
Psychological repression
Gene
030304 developmental biology
Cell lineage
Promoter
General Chemistry
Histone-Lysine N-Methyltransferase
DNA Methylation
Embryo
Mammalian
Mice
Inbred C57BL
Protein Subunits
biology.protein
030217 neurology & neurosurgery
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021)
Nature Communications
ISSN: 2041-1723
Popis: Silencing of a subset of germline genes is dependent upon DNA methylation (DNAme) post-implantation. However, these genes are generally hypomethylated in the blastocyst, implicating alternative repressive pathways before implantation. Indeed, in embryonic stem cells (ESCs), an overlapping set of genes, including germline “genome-defence” (GGD) genes, are upregulated following deletion of the H3K9 methyltransferase SETDB1 or subunits of the non-canonical PRC1 complex PRC1.6. Here, we show that in pre-implantation embryos and naïve ESCs (nESCs), hypomethylated promoters of germline genes bound by the PRC1.6 DNA-binding subunits MGA/MAX/E2F6 are enriched for RING1B-dependent H2AK119ub1 and H3K9me3. Accordingly, repression of these genes in nESCs shows a greater dependence on PRC1.6 than DNAme. In contrast, GGD genes are hypermethylated in epiblast-like cells (EpiLCs) and their silencing is dependent upon SETDB1, PRC1.6/RING1B and DNAme, with H3K9me3 and DNAme establishment dependent upon MGA binding. Thus, GGD genes are initially repressed by PRC1.6, with DNAme subsequently engaged in post-implantation embryos.
Germline genes are repressed by DNA methylation and histone marks. Here, the authors show that specific germline genes hypomethylated pre-implantation are enriched for PRC1.6, H2AK119ub1 and H3K9me3, which coordinately repress their expression.
Databáze: OpenAIRE
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