title: TRIM28 is required by the mouse KRAB domain protein ZFP568 to control convergent extension and morphogenesis of extra-embryonic tissues.
abstract: TRIM28 is a transcriptional regulator that is essential for embryonic development and is implicated in a variety of human diseases. The roles of TRIM28 in distinct biological processes are thought to depend on its interaction with factors that determine its DNA target specificity. However, functional evidence linking TRIM28 to specific co-factors is scarce. chatwo, a hypomorphic allele of Trim28, causes embryonic lethality and defects in convergent extension and morphogenesis of extra-embryonic tissues. These phenotypes are remarkably similar to those of mutants in the Krüppel-associated box (KRAB) zinc finger protein ZFP568, providing strong genetic evidence that ZFP568 and TRIM28 control morphogenesis through a common molecular mechanism. We determined that chatwo mutations decrease TRIM28 protein stability and repressive activity, disrupting both ZFP568-dependent and ZFP568-independent roles of TRIM28. These results, together with the analysis of embryos bearing a conditional inactivation of Trim28 in embryonic-derived tissues, revealed that TRIM28 is differentially required by ZFP568 and other factors during the early stages of mouse embryogenesis. In addition to uncovering novel roles of TRIM28 in convergent extension and morphogenesis of extra-embryonic tissues, our characterization of chatwo mutants demonstrates that KRAB domain proteins are essential to determine some of the biological functions of TRIM28.
authors: Department of Molecular Biology and Genetics, Cornell University, 526 Campus Road, Ithaca, NY 14853, USA.
authors: Maho
authors: M
authors: Shibata
authors: Kristin E
authors: KE
authors: Blauvelt
authors: Karel F
authors: KF
authors: Liem
authors: María J
authors: MJ
authors: García-García
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D005775:Gastrula / Q000378:metabolism; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D055550:Protein Stability; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C533182:Zfp568 protein, mouse; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28