The Murine Gene, Traube, Is Essential for the Growth of Preimplantation Embryos

Abstract

Little is known about the genetic control of preimplantation development. We have isolated, characterized, and mutated a previously undescribed mouse gene, Traube (Trb), essential for preimplantation development. Similar protein coding sequences are found in rats, humans, and yeast. The TRB protein contained two amino-terminal acidic domains, a leucine zipper, and three putative nuclear localization signals. The Trb gene was expressed at low levels ubiquitously early in development and became restricted to the liver and the central nervous system from E11.5 onward. Myc-tagged TRB protein was localized to the nucleus, and in a large proportion of the cells to the nucleoli. The Trb mutant embryos halted in development at the compacted morula stage at E2.5. At E3.5 they started to decompact and a day later they disintegrated and died. The observed defect was cell autonomous, as mutant cells failed to participate in the formation of chimeric embryos. The Trb mutant embryos showed a 50% reduction of the total cell number. The mutant embryos exhibited a paucity of ribosomes, polyribosomes, and rough endoplasmic reticulum. This paucity of ribosomes together with the localization of TRB to the nucleoli, the site of ribosome synthesis, suggests that TRB is involved in the synthesis of ribosomes.

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

“…MOZ and MORF are large proteins (B250 kDa) and possess intrinsic HAT activity attributable to their MYST domains (Champagne et al, 1999(Champagne et al, , 2001Thomas et al, 2000;Kitabayashi et al, 2001a). Both histones H3 and H4 are the substrates in vitro.…”

“…In addition, MOZ functions as a co-activator of the Nrf2-MafK heterodimer to upregulate the expression of GSTP (glutathione S-transferase placental form), a detoxification enzyme, during hepatocarcinogenesis (Ohta et al, 2007). Both MOZ and MORF are widely expressed in various mouse and human tissues (Borrow et al, 1996;Champagne et al, 1999;Thomas et al, 2000Thomas et al, , 2006Katsumoto et al, 2006), so similar to GCN5/PCAF and p300/CBP, they may function as co-activators for many transcription factors. This interesting possibility awaits further investigation.…”

ZIP kinase plays a crucial role in androgen receptor-mediated transcription

“…We have recently identified apoptosis antagonizing transcription factor (AATF) as a novel co-activator of nuclear receptors (Leister et al, 2003). AATF, also termed Che-1 (Fanciulli et al, 2000) or Traube (Thomas et al, 2000), was discovered as an interaction partner of Dlk/ZIPK (DAP-like kinase/ zipper interacting protein kinase) (Page et al, 1999b), of RNA polymerase II subunit 11 and of the retinoblastoma protein Rb (Fanciulli et al, 2000). The precise biological function of AATF remains to be elucidated.…”

The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase

“…In Drosophila, MOF (male-absent on the first) has been characterized (Akhtar and Becker, 2000;Hil®ker et al, 1997). In humans, there are hMOF (Neal et al, 2000), TIP60 (HIV Tat-interacting 60 kDa protein) (Yamamoto and Horikoshi, 1997), HBO1 (HAT bound to ORC 1) (Iizuka and Stillman, 1999), MOZ (Borrow et al, 1996), and MORF (Champagne et al, 1999;Thomas et al, 2000). ESA1, SAS3, MOF, TIP60, HBO1 and MORF have been shown to possess intrinsic HAT activity (Akhtar and Becker, 2000;Champagne et al, 1999;Iizuka and Stillman, 1999;John et al, 2000;Neal et al, 2000;Smith et al, 1998Smith et al, , 1999Takechi and Nakayama, 1999;Thomas et al, 2000;Yamamoto and Horikoshi, 1997).…”

“…In humans, there are hMOF (Neal et al, 2000), TIP60 (HIV Tat-interacting 60 kDa protein) (Yamamoto and Horikoshi, 1997), HBO1 (HAT bound to ORC 1) (Iizuka and Stillman, 1999), MOZ (Borrow et al, 1996), and MORF (Champagne et al, 1999;Thomas et al, 2000). ESA1, SAS3, MOF, TIP60, HBO1 and MORF have been shown to possess intrinsic HAT activity (Akhtar and Becker, 2000;Champagne et al, 1999;Iizuka and Stillman, 1999;John et al, 2000;Neal et al, 2000;Smith et al, 1998Smith et al, , 1999Takechi and Nakayama, 1999;Thomas et al, 2000;Yamamoto and Horikoshi, 1997). The function of this family of proteins is rather diverse, including roles in transcription, epigenetic control, DNA replication and repair (Akhtar and Becker, 2000;Galarneau et al, 2000;Iizuka and Stillman, 1999;Ikura et al, 2000;John et al, 2000;Reifsnyder et al, 1996;Smith et al, 1999).…”