Transient transcription in early embryo — sets up an epigenetic state that programs postnatal growth

The potential for “what happens during early embryonic events to program epigenetic states –– that influence adult physiology” –– remains an important question in health and vertebrate development. In the attached report, authors have chosen the imprinted Zdbf2 locus (zinc-finger DBF-type-containing-2) as a paradigm for studying early programming of traits in the embryo.

Authors show chromatin changes –– that occur in the pluripotent embryo –– can be dispensable for embryogenesis, whereas these changes represent “signal essential regulatory information” in the adult mouse. Authors found that the Liz (long isoform of Zdbf2) transcript is transiently expressed in early embryos and embryonic stem cells (ESCs). This transcription locally promotes de novo DNA methylation upstream of the Zdbf2 promoter –– which then antagonizes Polycomb-mediated repression of Zdbf2.  Intriguingly, Liz(–/–) mouse embryos, deficient for Liz, develop normally but fail to activate Zdbf2 in the postnatal brain and show indelible growth reduction.  This finding implies a crucial role for a Liz-dependent epigenetic switch. Hence, it appears that transcription –– during an early embryonic time frame –– can program a stable epigenetic state which has later physiological consequences.

Nat Genet  Jan 2o17; 49: 110-118

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