High-mobility group proteins 14 and 17 maintain the timing of early embryonic development in the mouse

The high-mobility group (HMG) proteins 14 and 17 are abundant chromosomal p roteins that bind to nucleosomes and enhance transcription. We report that both mRNA species and both proteins are present throughout oogenesis and pr eimplantation development of the mouse. When antisense oligonudeotides targ eting each mRNA species are injected into one-cell embryos, the proteins be come depleted at the two- and four-cell stages and reaccumulate at the eigh t-cell stage. One-cell embryos injected with antisense oligonucleotides tar geting both HMG-14 and HMG-17 cleave to the two-cell stage. Subsequent clea vages, however, are delayed compared with control-injected embryos. Neverth eless, these embryos ultimately reach the blastocyst stage. Similarly, inje ction into the nuclei of two-cell embryos of a peptide corresponding to the common nucleosome-binding domain of HMG-14 and HMG-17 delays progression t o the four-cell stage. Furthermore, both RNA and protein synthesis is trans iently reduced in antisense-injected embryos compared with injected control s. These results identify HMG-14 and HMG-17 as constitutive components of m ouse oocyte and embryonic chromatin and establish a link between the struct ure of embryonic chromatin and the normal progression of embryonic developm ent. (C) 2001 Academic Press.