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Provided is a method of nuclear reprogramming of a mammalian somatic cell to an iPS cell, comprising a step of contacting the mammalian somatic cell with a synthetic transcription factor that activates expression of a pluripotency factor gene (oct3/4, sox2, klf4, c-myc, lin28, nanog, glis-1, hcI2, and bclx), wherein the synthetic transcription factor comprises (i) at least one guide RNA comprising a DNA-binding segment to a promoter region of the pluripotency factor gene, and a polypeptide-binding segment, and (ii) at least one transcriptional modulator which binds said polypeptide-binding segment of said guide RNA. In a preferred embodiment, the said transcriptional modulator comprises an enzymatically inactive Cas9 polypeptide (dCas9) which is fused to a transcriptional activation domain VP64 or p65.