Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells.
The first wave of transcription, called zygotic genome activation (ZGA), begins during the 2-cell stage in mouse preimplantation development and marks a vital transition from the maternal genetic to the embryonic genetic program. Utilizing DNA microarray data, we looked for genes that are expressed only during ZGA and found Zscan4, whose expression is restricted to late 2-cell stage embryos. Sequence analysis of genomic DNA and cDNA clones revealed nine paralogous genes tightly clustered in 0.85 Mb on mouse chromosome 7. Three genes are not transcribed and are thus considered pseudogenes. Among the six expressed genes named Zscan4a-Zscan4f, three - Zscan4c, Zscan4d, and Zscan4f - encode full-length ORFs with 506 amino acids. Zscan4d is a predominant transcript at the late 2-cell stage, whereas Zscan4c is a predominant transcript in embryonic stem (ES) cells. No transcripts of any Zscan4 genes are detected in any other cell types. Reduction of Zscan4 transcript levels by siRNAs delays the progression from the 2-cell to the 4-cell stage and produces blastocysts that fail to implant or proliferate in blastocyst outgrowth culture. Zscan4 thus seems to be essential for preimplantation development.
Falco
Geppino
G
Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Lee
Sung-Lim
SL
Stanghellini
Ilaria
I
Bassey
Uwem C
UC
Hamatani
Toshio
T
Ko
Minoru S H
MS
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002970:Cleavage Stage, Ovum / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D051379:Mice; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D017931:DNA Primers; D018076:DNA, Complementary; D034741:RNA, Small Interfering; D014157:Transcription Factors; C534888:Zscan4d protein, mouse