HUB1, a novel Kruppel type zinc finger protein, represses the human T cell leukemia virus type I long terminal repeat-mediated expression

Abstract

We have shown that human T-cell leukemia virus type I (HTLV-I) gene expression is negatively regulated by the U5 repressive element (U5RE) of its long terminal repeat (LTR). To isolate factors binding to U5RE, we screened a cDNA expression library by south-western blotting with a U5RE probe. Screening 2 x10(6) clones gave a positive clone with a 3.8 kb insert encoding a novel 671 residue polypeptide, named HTLV-I U5RE binding protein 1 (HUB1), with five zinc finger domains and a Krüppel-associated box like domain; HUB1 may be related to a repressor belonging to the Krüppel type zinc finger protein. A 4.0 kb mRNA for HUB1 is ubiquitously expressed among all human tissues tested. HUB1 recognizes the TCCACCCC sequence as a core motif and exerts a strong repressive effect on HTLV-I LTR-mediated expression. A new repressive domain, named HUB1 repressive (HUR) domain, was identified, rather than the Krüppel-associated box like domain. The N-terminal region upstream of HUR domain seemed to be also indispensable to the repression. Thus, we propose that HUB1 is a new type repressor and plays an important role in the HTLV-I U5-mediated repression.

Zic1 is a Transcriptional Repressor Through the Lamin A/C Promoter and has an Intrinsic Repressive Domain

“…16) Other zinc finger transcriptional factors, such as Sp3 and HUB1, also have activating and repressive domains, which allow them to either activate or inhibit gene transcription. 19,20) Interestingly, Zic1 binds the same L-RARE sequence as Sp1, suggesting Zic1 may modulate other transcription factors by both direct interaction and by blocking their binding at the promoter.…”

A Novel Zinc Finger Transcription Factor with Two Isoforms That Are Differentially Repressed by Estrogen Receptor-α

“…The KRAB domains are common features of many zinc finger proteins and are associated with transcriptional regulation. The region of p71-ZER6 that is not contained in the p52 isoform demonstrated a region of striking homology with HUB-1 (16). Over a region of 139 amino acids (from amino acid 33 to 171), there is 74% identity and 84% homology with the HUB-1 repressor domain.…”

“…In addition, each of the linkers between the Cys 2 residues comprises two amino acids. A BLASTp search of the protein sequence unique to p71-ZER6 matched a region of a zinc finger protein that had extensive homology with a repression domain called HUB-1 (16). The HUB-1 domain was shown to be functionally important for repression of human T-cell lymphotrophic virus type I long terminal repeat-mediated expression.…”

“…Transcripts from the ZER6 gene have alternative 5Ј exons, which encode two related iso-forms: p71-ZER6 and p52-ZER6. The p71 isoform contains a HUB-1 domain, which was previously identified to be important for repression of long terminal repeat-mediated transactivation (16). The p52 isoform of ZER6 interacts strongly with ER␣ in the presence of 17␤-estradiol, whereas the p71 isoform demonstrated no binding to ER␣.…”

Erase–Maintain–Establish: Natural Reprogramming of the Mammalian Epigenome

“…ZFP57 plays a conserved role in imprinting maintenance in humans and mice. Diverse ZFPs/ZFNs (mouse/human) are involved in retrovirus silencing and other physiological functions (Okumura et al 1997;Zheng et al 2000;Li et al 2008;Takahashi et al 2009;Wolf and Goff 2009;Quenneville et al 2011;Nishitsuji et al 2012Nishitsuji et al , 2015Tan et al 2013;Castro-Diaz et al 2014;Jacobs et al 2014;Wolf et al 2015b). (Messerschmidt 2012;Messerschmidt et al 2012).…”