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PMID:24036311

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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

Significance

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

Notes

See also

References

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