TBP2, a Vertebrate-Specific Member of the TBP Family, Is Required in Embryonic Development of Zebrafish

Abstract

TATA binding protein (TBP) is a key regulator of RNA polymerase transcription. It binds to core promoters, often in large multiprotein complexes, and nucleates RNA polymerase II (Pol II) transcription initiation. In addition to the previously described TBP-like factor present in metazoans (TLF/TRF2/TRP/TLP), we describe a third, vertebrate-specific member of the TBP protein family from zebrafish, called TBP2. Evolutionary conserved TBP2 homologs were also found in human, mouse, frog, and pufferfish. The N-terminal domains of TBP2s are divergent amongst themselves and different from those of TBPs; however, the core domain of TBP2s and TBPs are almost identical. TBP2 binds the TATA box, interacts with TFIIA and TFIIB (similarly to TBP), and can mediate Pol II transcription initiation. However, TBP2 shows contrasting expression patterns in the gonads and during embryonic development in comparison to TBP, suggesting differential function. Knockdown of zebrafish TBP2 results in specific reduction of the protein level, leading to a phenotype, which indicates the requirement of TBP2 for embryonic patterning. The presence of three different TBP family members in vertebrates suggests the existence of developmental stage- and tissue-specific preinitiation complexes with specific requirements for different TBP family members.

TRF2: TRansForming the view of general transcription factors

“…51 TRF3 (also known as TBP2 (TATA-binding protein 2) and TBPL2 (TBP-like protein 2)), which is the TRF that is most closely related to TBP, is unique to vertebrates. [52][53][54][55] Similarly to TBP and TRF1, TRF3 can associate with TFIIA and TFIIB. 52,54 TRF3 binds TATA-box containing promoters and activates them.…”

“…[52][53][54][55] Similarly to TBP and TRF1, TRF3 can associate with TFIIA and TFIIB. 52,54 TRF3 binds TATA-box containing promoters and activates them. TRF3 has been shown to be important for initiation of hematopoiesis during zebrafish embryogenesis.…”

“…Importantly, TRF3 of Xenopus and zebrafish is mainly expressed in oocytes and is essential for embryogenesis. 52,54 Mouse TRF3, which is exclusively expressed in oocytes, is essential for the differentiation of female germ cells but not for embryonic development. 59 TRF2 is the TRF protein with the least similarity to TBP.…”

Regulated expression of TATA-binding protein-related factor 3 (TRF3) during early embryogenesis

“…In addition, TRF3 proceeds through most phases of the cell cycle at a pace parallel to TBP, except Telophase-E, when TRF3 was slightly delayed in entering the nucleus. Based on the fact that (1) TRF3 has a conserved C-terminal region and a DNA-binding domain virtually identical to TBP [20,21], (2) TRF3 can mediate transcription initiation in both HeLa cell extract and Xenopus egg extract [20,22], (3) TRF3 is co-expressed with TBP during early development, and its dynamic change correlates well with transcriptional activity (Figures 1 and 2), (4) both factors proceed through most cell cycle phases at a similar pace (Figure 3), and (5) TRF3 binds to the promoter(s) of genes that are expressed in early embryogenesis (Figure 4), we suggest that TRF3 may play a role in early embryonic development. Our results support the proposal that TRF3 is a possible candidate for TBP-independent transcription in the TBP −/− cells [20,22].…”

“…However, TRF2 is neither expressed [17] nor required for mouse embryogenesis [18,19]. More recently, a fourth member of the TBP family named TRF3 (also called TBP2) has been reported [20][21][22]. TRF3 has a highly conserved C-terminal domain, which is 96% conserved with TBP, and a non-conserved N-terminal domain that is 31% conserved.…”