Delta, a transcription factor that binds to downstream elements in several polymerase II promoters, is a functionally versatile zinc finger protein.

Abstract

The promoters of several eukaryotic genes transcribed by RNA polymerase H contain elements located downstream of the transcriptional start site. To gain insight into how these elements function in the formation of an active transcription complex, we have cloned and sequenced the cDNA that encodes 8, a protein that binds to critical downstream promoter elements in the mouse ribosomal protein rpL30 and rpL32 genes. Our results revealed that the 6 protein contains four C-terminal zinc fingers, which are essential for its DNA binding capability and a very unusual N-terminal domain that includes stretches of 11 consecutive negatively charged amino acids and 12 consecutive histidines. The sequence of the 8 protein was found to be essentially identical to a concurrently cloned human transcription factor that acts both positively and negatively in the context of immunoglobulin enhancers and a viral promoter. Our structural modeling of this protein indicates properties that could endow it with exquisite functional versatility.that encodes a protein termed 6, which binds to critical downstream elements in the genes encoding mouse ribosomal proteins L30 and L32 (rpL30 and rpL32) (Fig. 1A) and to downstream elements of several other genes, as inferred from sequence comparisons of functionally important factor binding sites (Fig. 1B) and a direct competition assay (10).tAt the completion of this study, we learned that the 6 sequence is almost identical to that of a human transcription factor that can act either negatively or positively in the context of the immunoglobulin K 3' and heavy-chain enhancers (13) and the P5 promoter of adeno-associated virus (14). The properties of this protein apparently suit it to function with downstream promoter elements, as well as to perform both activating and repressive functions. Our results have revealed that 8 is a zinc finger protein with unusual structural features that could endow it with exquisite functional versatility.The transcription of eukaryotic genes by RNA polymerase II is regulated by an interplay of sequence-specific activator or repressor factors and essentially nonspecific general factors and chromatin components (1). The specific factors recognize sequence modules or elements that are situated both in promoters-i.e., regions near the transcriptional start siteand in enhancers-i.e., regions distant from the start site. Specificity in transcriptional regulation is determined by the composition and organization of these elements and the availability of the factors that interact with them.A considerable effort is currently being made to understand the way in which sequence-specific and general factors interact during formation of active transcription complexes (2, 3). In most mechanistic studies of promoter function, major attention has been given to factors that bind to elements located upstream of the transcriptional start site. However, it has become increasingly evident that a large number of both cellular and viral genes utilize elements that are located downst...

Binding of YY1 to a Site Overlapping a Weak TATA Box Is Essential for Transcription from the Uteroglobin Promoter in Endometrial Cells

“…As a first step toward a precise description of this promoter element, in this study we identified the ubiquitous factor TPF as the transcription/initiation factor YY1. This 414-amino-acid Krüppel-like protein with four C 2 H 2 -type zinc fingers was cloned independently and in different contexts by four groups some years ago and is also referred to as ␦, NF-E1, and UCRBP (15,19,42,51). In the meantime, binding sites for YY1 have been identified in many promoters, indicating that this factor may be of general importance for transcription initiation from a substantial number of promoters.…”

“…YY1 (also called ␦, NF-E1, and UCRBP) is a 414-amino-acid Krüppel-like protein (15,19,42,51) that represses a variety of cellular as well as viral promoters but can also activate the expression of other genes (see reference 22 for further references), hence the designation YY1 (yin and yang 1). YY1 can also direct accurate basal transcription in vitro through the initiators of the cytochrome c oxidase subunit Vb promoter (4) and the adeno-associated virus (AAV) type 2 P5 promoter (50).…”

YY1 is indispensable for Lgr5 + intestinal stem cell renewal

“…YY1 is a zinc finger transcription factor first discovered for its function in viral gene expression (20,21) and cloned during investigations of viral (22), immunoglobulin (23), and ribosomal (24) gene expression. YY1 has since been implicated in a number of processes, including development of muscle (25)(26)(27)(28)(29)(30) and B cells (31)(32)(33), and stem cell regulation (34)(35)(36)(37).…”

Functional analysis of the promoter region of the human phosphotyrosine phosphatase activator gene: Yin Yang 1 is essential for core promoter activity

“…A large number of cellular and viral genes have been shown to be negatively regulated by YY1 (for reviews, see [31,34]). Examples of genes positively regulated by YY1 include c-myc [35], some ribosomal protein genes [36] and p53 [37].…”