Induction of early transcription in one-cell mouse embryos by microinjection of the nonhistone chromosomal protein HMG-I

In the mouse embryo, the onset of zygotic transcription occurs at the end o f the first cell cycle, upon completion of DNA replication. We show that th e nonhistone chromosomal protein HMG-I, whose translocation into the pronuc lei of one-cell embryos is linked to this first round of DNA synthesis, pla ys a critical role in the activation of zygotic transcription. Indeed, micr oinjection of purified HMG-I results in a higher nuclear accumulation of th e protein and triggers an earlier activation of zygotic transcription, an e ffect which is abolished by the preincubation of the protein with a specifi c antibody directed against its AT-hook DNA-binding motifs. Significantly, microinjection of this antibody also prevents the normal onset of transcrip tion in the embryo, suggesting that endogenous HMG-I is similarly involved in this process. Finally, microinjection of the exogenous protein modifies chromatin structure as measured by in situ accessibility to DNase I. We pro pose that general chromosomal architectural factors such as HMG-I can modul ate the accessibility of chromatin to specialized regulatory factors, there by promoting a transcriptionally competent state, (C) 2000 Academic Press.