Transcriptional repression of the c-fos gene by YY1 is mediated by a direct interaction with ATF/CREB

Abstract

Transcriptional activation of the mouse c-fos gene by the adenovirus 243-amino-acid E1A protein requires a binding site for transcription factor YY1 located at ؊54 of the c-fos promoter. YY1 normally represses transcription of c-fos, and this repression depends on the presence of a cyclic AMP (cAMP) response element located immediately upstream of the ؊54 YY1 DNA-binding site. This finding suggested that the mechanism of transcriptional repression by YY1 might involve a direct interaction with members of the ATF/CREB family of transcription factors. In vitro and in vivo binding assays were used to demonstrate that YY1 can interact with ATF/CREB proteins, including CREB, ATF-2, ATFa1, ATFa2, and ATFa3. Structure-function analyses of YY1 and ATFa2 revealed that the C-terminal zinc finger domain of YY1 is necessary and sufficient for binding to ATFa2 and that the basic-leucine zipper region of ATFa2 is necessary and sufficient for binding to YY1. Overexpression of YY1 in HeLa cells resulted in repression of a mutant c-fos chloramphenicol acetyltransferase reporter that lacked binding sites for YY1, suggesting that repression can be triggered through protein-protein interactions with ATF/CREB family members. Consistent with this finding, repression was relieved upon removal of the upstream cAMP response element. These data support a model in which YY1 binds simultaneously to its own DNA-binding site in the c-fos promoter and also to adjacent DNA-bound ATF/CREB proteins in order to effect repression. They further suggest that the ATF/CREB-YY1 complex serves as a target for the adenovirus 243-amino-acid E1A protein.

DNA methylation and Yin Yang‐1 repress adenosine A2A receptor levels in human brain

“…Further analyses are needed to elucidate the mechanism of action of YY1 in relation to brain-specific region ADORA2A expression. For instance, it needs to be examined whether it forms a repression complex with histone deacetylase (HDAC)1/2 (Thomas and Seto 1999), or whether it interacts with cAMPresponse element binding protein, interfering with its positive role above cerebellar ADORA2A expression (Zhou et al 1995;Chiang et al 2005). Interestingly, the formation of YY1/ZBP-89 complex, reducing the ability of ZBP-89 to activate gene expression, has been described (Boopathi et al 2004).…”

Identification of YY1 sequences necessary for association with the nuclear matrix and for transcriptional repression functions

“…A number of proteins are known to physically interact with YY1, some within the zinc finger region. These YY1 interacting proteins include TBP, CBP, p300, TFIIB, c-myc, Sp1, ATF2, CREB, AP1, TAFII 55 , and E1A [Usheva and Shenk, 1994, Chiang and Roeder, 1994Seto et al, 1993;Zhou et al, 1995;O'Connor et al, 1996;Shrivastava et al, 1993;Yang et al, 1996;Austen et al, 1997;Shi et al, 1991]. YY1 sequences 333-371 could potentially inhibit enhancer activity by physically interacting with one or more of these proteins thereby disrupting transcriptional activity.…”

“…Protein interactions with YY1 can also lead to loss of activated transcription. For instance, interaction of YY1 with transcriptional activators such as ATF/ CREB and AP1 can lead to loss of activated transcription [Zhou et al, 1995;O'Connor et al, 1996]. In addition, YY1 can repress human papilloma virus type 16 transcription by quenching AP1 activity [O'Connor et al, 1996].…”

Point mutation in calcium-binding domain of mouse polyomavirus VP1 protein does not prevent virus-like particle formation, but changes VP1 interactions with cell structures

“…Looking for a mammalian functional equivalent of the unknown VP1-binding transcription factor of yeast, we had discovered the direct interaction of VP1 with the pleiotropic transcription regulator, YY1 [31]. Zhou et al [32] have suggested that the YY1 -ATF/CREB complex serves as a target for the adenovirus E1A 243 protein. Members of the mammalian ATF/CREB family of transcription factors are associated with regulation by cAMP.…”