Tzfp Represses the Androgen Receptor in Mouse Testis

Kari Furu,Arne Klungland,Pierre-Antoine Defossez

doi:10.1371/journal.pone.0062314

Kari Furu, Arne Klungland + Show 1 more

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https://doi.org/10.1371/journal.pone.0062314

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Journal: PloS one	Publication Date: Apr 25, 2013
Citations: 12	License type: CC BY 4.0

Affiliation: Oslo University Hospital, University of Oslo

Abstract

The testis zinc finger protein (Tzfp), also known as Repressor of GATA, belongs to the BTB/POZ zinc finger family of transcription factors and is thought to play a role in spermatogenesis due to its remarkably high expression in testis. Despite many attempts to find the in vivo role of the protein, the molecular function is still largely unknown. Here, we address this issue using a novel mouse model with a disrupted Tzfp gene. Homozygous Tzfp null mice are born at reduced frequency but appear viable and fertile. Sertoli cells in testes lacking Tzfp display an increase in Androgen Receptor (AR) signaling, and several genes in the testis, including Gata1, Aie1 and Fanc, show increased expression. Our results indicate that Tzfp function as a transcriptional regulator and that loss of the protein leads to alterations in AR signaling and reduced number of apoptotic cells in the testicular tubules.

Highlights

The Testis Zinc Finger Protein (Tzfp), known as Repressor of GATA, is a transcription factor belonging to the BTB/POZ-ZF (Broad complex, Tramtrack, Brick abrack (BTB) or poxvirus and zinc finger (POZ)-zinc finger) protein family [1,2]
In the present study we show that removal of the Tzfp protein is not lethal, but that breeding mice heterozygous and homozygous for the gene trap insertion yields fewer TzfpGTi/GTi pups than expected, indicating decreased survival of Tzfp deficient embryos
Lack of Tzfp leads to increased lymphocyte proliferation and increased cytokine production upon antigen stimulation [8,7], whereas enforced expression is associated with decreased cytokine production and accumulation in the G1 phase of the cell cycle followed later by apoptosis [13,9]

Summary

Introduction

The Testis Zinc Finger Protein (Tzfp), known as Repressor of GATA, is a transcription factor belonging to the BTB/POZ-ZF (Broad complex, Tramtrack, Brick abrack (BTB) or poxvirus and zinc finger (POZ)-zinc finger) protein family [1,2]. The BTB/ POZ-ZF proteins generally function as transcription regulators and are involved in a broad range of biological processes, including cell survival and differentiation [3,4]. Tzfp is homologous to another BTB/POZ-ZF protein, Plzf (promyelocytic leukemia zinc finger protein). BLAST analysis reveals over 50% identity, with the highest similarity in the zinc finger domain. PLZF is regarded as a tumor suppressor and works as a transcriptional repressor and chromatin remodeller implicated in cancer and the self-renewal of spermatogonial stem cells [5,6]

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