4.5 Article

Involvement of a novel preimplantation-specific gene encoding the high mobility group box protein Hmgpi in early embryonic development

Journal

HUMAN MOLECULAR GENETICS
Volume 19, Issue 3, Pages 480-493

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddp512

Keywords

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Funding

  1. Japan Society for the Promotion of Science [19591911, 21390456]
  2. Japanese Ministry of Health, Labor, and Welfare [H21-001, H20-001, H18-004]
  3. Yamaguchi-Endocrine Organization
  4. [21791581]
  5. Grants-in-Aid for Scientific Research [19591911, 21791581] Funding Source: KAKEN

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Mining gene-expression-profiling data identified a novel gene that is specifically expressed in preimplantation embryos. Hmgpi, a putative chromosomal protein with two high-mobility-group boxes, is zygotically transcribed during zygotic genome activation, but is not transcribed postimplantation. The Hmgpi-encoded protein (HMGPI), first detected at the 4-cell stage, remains highly expressed in pre-implantation embryos. Interestingly, HMGPI is expressed in both the inner cell mass (ICM) and the trophectoderm, and translocated from cytoplasm to nuclei at the blastocyst stage, indicating differential spatial requirements before and after the blastocyst stage. siRNA (siHmgpi)-induced reduction of Hmgpi transcript levels caused developmental loss of preimplantation embryos and implantation failures. Furthermore, reduction of Hmgpi prevented blastocyst outgrowth leading to generation of embryonic stem cells. The siHmgpi-injected embryos also lost ICM and trophectoderm integrity, demarcated by reduced expressions of Oct4, Nanog and Cdx2. The findings implicated an important role for Hmgpi at the earliest stages of mammalian embryonic development.

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