PMID:24036311

Citation	Zhang, K, Haversat, JM and Mager, J (2013) CTR9/PAF1c regulates molecular lineage identity, histone H3K36 trimethylation and genomic imprinting during preimplantation development. Dev. Biol. 383:15-27
Abstract	Genome-wide epigenetic reprogramming is required for successful preimplantation development. Inappropriate or deficient chromatin regulation can result in defective lineage specification and loss of genomic imprinting, compromising normal development. Here we report that two members of the RNA polymerase II associated factor, homolog (Saccharomyces cerevisiae) complex (PAF1 complex) components, Ctr9 and Rtf1, are required during mammalian preimplantation development. We demonstrate that Ctr9-deficient embryos fail to correctly specify lineages at the blastocyst stage. Expression of some lineage specific factors is markedly reduced in Ctr9 knockdown embryos, including Eomes, Elf5 and Sox2, while others are inappropriately expressed (Oct4, Nanog, Gata6, Fgf4 and Sox17). We also show that several imprinted genes (Mest, Peg3, Snrpn and Meg3) are aberrantly expressed although allele specific DNA methylation is not altered. We document a loss of histone H3 lysine 36 trimethylation (H3K36me3) in Ctr9-deficient embryos and confirm that knockdown of either Setd2 or Rtf1 results in similar phenotypes. These findings show that the PAF1 complex is required for mammalian development, likely through regulation of H3K36me3, and indicate functional conservation of the PAF1 complex from yeast to mammals in vivo.
Links	PubMed Online version:10.1016/j.ydbio.2013.09.005
Keywords	Animals; Base Sequence; Carrier Proteins/metabolism; Cell Lineage/physiology; DNA Methylation; DNA Primers/genetics; Embryonic Development/physiology; Epigenesis, Genetic/physiology; Fluorescent Antibody Technique; Gene Expression Regulation, Developmental/physiology; Genomic Imprinting/physiology; Histones/metabolism; Mice; Microinjections; Molecular Sequence Data; RNA, Double-Stranded/biosynthesis; Real-Time Polymerase Chain Reaction; Sequence Analysis, DNA
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:RTF1	involved_in	GO:0001832: blastocyst growth	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:SETD2	involved_in	GO:0097198: histone H3-K36 trimethylation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:CADH1	located_in	GO:0005911: cell-cell junction	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:PO5F1	involved_in	GO:0001832: blastocyst growth	ECO:0000316: genetic interaction evidence used in manual assertion	MGI:MGI:109345	P		Seeded From UniProt	complete
MOUSE:CDX2	located_in	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:SOX2	located_in	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:GATA6	located_in	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:CTR9	located_in	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:CTR9	involved_in	GO:0001832: blastocyst growth	ECO:0000316: genetic interaction evidence used in manual assertion	MGI:MGI:101893	P		Seeded From UniProt	complete
MOUSE:CTR9	involved_in	GO:2000653: regulation of genetic imprinting	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:CTR9	involved_in	GO:0001826: inner cell mass cell differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:CTR9	involved_in	GO:0001829: trophectodermal cell differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:CTR9	involved_in	GO:0001832: blastocyst growth	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:NANOG	located_in	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:PO5F1	acts_upstream_of_or_within	GO:0001832: blastocyst growth	ECO:0000316: genetic interaction evidence used in manual assertion	MGI:MGI:109345	P		Seeded From UniProt	complete
MOUSE:CADH1	part_of	GO:0005911: cell-cell junction	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:SOX2	part_of	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete

References

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