YY1AP, A Novel Co-activator of YY1

Abstract

With the aim of identifying potential cellular proteins that mediate the transcriptional regulation of YY1, a HeLa cDNA library was screened using the yeast twohybrid system. A previously unknown protein interacting with YY1 was identified and named YY1AP. By using the 5-rapid amplification of cDNA ends technique, the full-length cDNA of YY1AP was cloned and sequenced. The cDNA was 2253 bp in length and encoded an open reading frame of 750 amino acids. The chromosomal gene was made up of 10 exons separated by nine introns and is localized on chromosome 1 (1q21.3). Northern blot analysis revealed that YY1AP is ubiquitously expressed in various human tissues and cancer cell lines. Co-immunoprecipitation and immunostaining of cells further indicated that YY1AP co-localizes with YY1 in the nucleus. Furthermore, YY1AP was shown to be capable of enhancing the transcriptional activation of an YY1 responsive promoter. Subsequent analysis by glutathione S-transferase pull-down assay showed that YY1AP contained two YY1 binding regions. The transactivation region of YY1AP would seem to be localized within the section of amino acids 260 -345. It is proposed that YY1AP is a novel co-activator of YY1.YY1 is a 65-kDa multifunctional zinc finger transcription factor that belongs to the human GLI-Krü ppel family of nuclear proteins (1-6). It is expressed in a wide variety of different cell types and shows a high degree of sequence similarity among divergent organisms (7,8). The YY1 protein contains four C-terminal zinc finger domains with the capability of DNA binding, one transcription activation domain at the N terminus, and two repression domains (7, 9). It can bind to the specific DNA consensus sequence 5Ј-CGCCATNTT-3Ј, which is present in many promoters, and regulates transcription activity by either activation or repression (1, 10, 11). Some domains of YY1 are used to mediate interaction with other proteins and regulated transcription activity via YY1 binding to the consensus sequence on promoter (12). Several studies have revealed that YY1 is subject to complex regulatory mechanisms in different cell types (13). The modulation that occurs at different promoters is because of the various components of YY1 complex that are present. As an activator, a repressor, or an initiator, the function of YY1 in transcription is context-specific and is regulated by its interactions with various cellular factors and adaptor proteins (5,13,14). YY1 has been shown to interact physically with a number of cellular and viral proteins to modulate the expression of these genes. Thus, both the promoter context and the cellular environment influence YY1 activation (2, 4, 15).As a repressor, YY1 can repress several well characterized promoters such as c-fos, immunoglobulin 3Ј enhancer, skeletal ␣-actin, P5 promoter of adeno-associated virus, and murine leukemia virus long terminal repeat (1, 7, 12). There are three models to explain the repression function of YY1. First, YY1 acts via activator displacement through an overlapping DNA binding site ...

Action of Transcription Factors in the Control of Transferrin Receptor Expression in Human Brain Endothelium

“…34 YY1 is subject to complex regulatory mechanisms in different cell types which affect its functional activity. 35 The promoter sequences surrounding YY1 binding sites, 15 its relative concentration, 36 or post translational modifications, 37 can determine whether YY1 acts as a repressor or activator. In addition, since the binding motif of YY1 is present in a large number of genes, the regulation conferred by YY1 is probably modulated by association with other cell-type specific proteins, 31 including various cellular factors and adaptor proteins, 35 which are themselves, coactivators, corepressors or transcription factors.…”

Assembly of the Yin Yang 1 Transcription Factor into Messenger Ribonucleoprotein Particles Requires Direct RNA Binding Activity

“…The activity of YY1 is modified by numerous interactions with other proteins, including c-Myc (4), Sp1 (5,6), the polycomb group protein EED (7), cAMPresponse element-binding protein (8), the viral protein E1A (9), retinoblastoma protein (10), the GATA1 transcription factor (11), and the specific activator YY1AP (12). YY1 is subject to post-translational modifications such as glycosylation (13), acetylation (14), and phosphorylation (15).…”

Sustained Downregulation of YY1-Associated Protein-Related Protein Gene Expression in Rat Hippocampus Induced by Repeated Electroconvulsive Shock

“…[1][2][3] In the YARP structure, various functional motifs are predicted, including nuclear localization signals and domains associated with protein-protein interactions, DNAbinding and chromatin assembly, found outside the YY1AP-homology domain. Therefore, YARP is suggested to be multifunctional and to play not only a role analogous to YY1AP, but also its own specific roles in DNA-utilizing processes such as transcription.…”

“…ECS was performed as reported previously. 5) Briefly, ECS was administered via ear-clip electrodes (35 mA, 0.5 s) to induce a typical clonic-tonic seizure lasting 5-10 s. In acute experiments, the animals were decapitated 1, 3,6,12,24,48, and 72 h after a single ECS. In chronic experiments, ECS was administered every other day, totaling six shocks.…”