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Molecular and Cellular Biology, March 2008, p. 1565-1572, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.01038-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Sizn1 Is a Novel Protein That Functions as a Transcriptional Coactivator of Bone Morphogenic Protein Signaling ^,

Ginam Cho,¹ Youngshin Lim,^1, Dina Zand,^2, and Jeffrey A. Golden^1,3*

Departments of Pathology,¹ Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,² Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania³

Received 12 June 2007/ Returned for modification 26 July 2007/ Accepted 12 December 2007

Bone morphogenic proteins (BMPs) play pleotrophic roles in nervous system development, and their signaling is highly regulated at virtually every step in the pathway. We have cloned a novel gene, Sizn1 (Smad-interacting zinc finger protein), which functions as a transcriptional coactivator of BMP signaling. It positively modulates BMP signaling by interacting with Smad family members and associating with CBP in the transcription complex. Sizn1 is expressed in the ventral embryonic forebrain, where, as we will show, it contributes to BMP-dependent, cholinergic-neuron-specific gene expression. These data indicate that Sizn1 is a positive modulator of BMP signaling and provide further insight into how BMP signaling can be modulated in neuronal progenitor subsets to influence cell-type-specific gene expression and development.

Published ahead of print on 26 December 2007.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 36th and Spruce Streets, Philadelphia, PA 19104-4283.

Present address: Division of Genetics and Metabolism, Children's National Medical Center, George Washington University Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010-2970.