Identification of mZnf8, a mouse Krüppel-like transcriptional repressor, as a novel nuclear interaction partner of Smad1.

Abstract:

:To identify novel genes that play critical roles in mediating bone morphogenetic protein (BMP) signal pathways, we performed a yeast two-hybrid screen using Smad1 as bait. A novel mouse Krüppel-type zinc finger protein, mZnf8, was isolated. Interactions between mZnf8 and Smad proteins were further analyzed with various in vitro and in vivo approaches, including mammalian two-hybrid, in vitro glutathione S-transferase pulldown, and copurification assays. Results from functional analysis indicate that mZnf8 is a nuclear transcriptional repressor. Overexpression of mZnf8 represses activity of BMP and transforming growth factor beta (TGF-beta) reporters. Silencing the expression of endogenous mZnf8 with an RNA interference approach caused a significant increase in the expression of one BMP reporter. These results suggest that mZnf8 negatively regulates the TGF-beta/BMP signaling pathway in vivo. Transcription of mZnf8 is ubiquitous in mouse embryos, but high levels are specifically observed in adult mouse testes, with the same cell- and stage-specific transcription pattern as Smad1. Our data support the hypothesis that mZnf8 plays critical roles in mediating BMP signaling during spermatogenesis.

journal_name

Mol Cell Biol

authors

Jiao K,Zhou Y,Hogan BL

doi

10.1128/mcb.22.21.7633-7644.2002

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

7633-44

issue

21

eissn

0270-7306

issn

1098-5549

journal_volume

22

pub_type

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