Analysis of overrepresented motifs in human core promoters reveals dual regulatory roles of YY1

Bioinformatics Program, Boston University, Boston, Massachusetts 02215, USA.
Genome Research (Impact Factor: 14.63). 07/2007; 17(6):798-806. DOI: 10.1101/gr.5754707
Source: PubMed


A set of 723 high-quality human core promoter sequences were compiled and analyzed for overrepresented motifs. Beside the two well-characterized core promoter motifs (TATA and Inr), several known motifs (YY1, Sp1, NRF-1, NRF-2, CAAT, and CREB) and one potentially new motif (motif8) were found. Interestingly, YY1 and motif8 mostly reside immediately downstream from the TSS. In particular, the YY1 motif occurs primarily in genes with 5'-UTRs shorter than 40 base pairs (bp) and its locations coincide with the translation start site. We verified that the YY1 motif is bound by YY1 in vitro. We then performed detailed analysis on YY1 chromatin immunoprecipitation data with a whole-genome human promoter microarray (ChIP-chip) and revealed that the thus identified promoters in HeLa cells were highly enriched with the YY1 motif. Moreover, the motif overlapped with the translation start sites on the plus strand of a group of genes, many with short 5'-UTRs, and with the transcription start sites on the minus strand of another distinct group of genes; together, the two groups of genes accounted for the majority of the YY1-bound promoters in the ChIP-chip data. Furthermore, the first group of genes was highly enriched in the functional categories of ribosomal proteins and nuclear-encoded mitochondria proteins. We suggest that the YY1 motif plays a dual role in both transcription and translation initiation of these genes. We also discuss the evolutionary advantages of housing a transcriptional element inside the transcript in terms of the migration of these genes in the human genome.

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    • "To investigate the cell signaling pathways that might be involved in the mitochondrial response to amino acid starvation, we studied two well-known energy and nutrient sensors AMP-activated protein kinase (AMPK) and TORC1 [6], [22], together with two recognized inducers of mitochondrial biogenesis, the transcription co-activator PGC1α [23], [24] and the transcription factor YY1 [23], [25]. Although there was an increase in active AMPK whenever amino acids were withdrawn from the growth medium, the extent of the increase was dependent on sugar availability (Fig. 5B). "
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    • "A homolog of YY1, the Drosophila PHO protein, is involved in Polycomb repression [52,53], but there is limited evidence for this in mammals, where YY1 is rather viewed as a global regulator. YY1 binding motifs are overrepresented in core promoters [54], with approximately 10% of human promoters containing it [55]. Additionally, YY1 is important for initiating transcription of various transposable elements such as LINE-1s [56,57], Alu SINEs [58], Herv-Ks [59] and LTRs [60]. "
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    • "It has been found to serve as a central component of the transcriptional regulatory circuity that coordinately controls the energy-generating functions of mitochondria (Figure 2). It is capable of driving transcriptional control of mitochondrial biogenesis through direct interaction with, and coactivation of, PPARs (Madrazo and Kelly, 2008), estrogen-related receptors (ERRs; Schreiber et al., 2004; Eichner and Giguère, 2011), nuclear respiratory factors (NRF-1/NRF-2; Wu et al., 1999; Scarpulla, 2011) and the transcription factor yin-yang one (YY1; Basu et al., 1997; Seelan and Grossman, 1997; Cunningham et al., 2007; Xi et al., 2007), which are important nuclear transcription factors controlling mitochondrial metabolism (Scarpulla et al., 2012). PGC-1α is also an inducible responder to cellular energetic and metabolic stress, such as cold exposure (Puigserver et al., 1998; Uldry et al., 2006; Fisher et al., 2012), nutrient deprivation (Herzig et al., 2001; Yoon et al., 2001; Handschin et al., 2005; Rhee et al., 2006) and exercise (Baar et al., 2002; Handschin and Spiegelman, 2008) and is dynamically regulated in response to a variety of signaling pathways involved in cellular growth, differentiation and energy metabolism. "
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