The three-dimensional organization of chromosomes can have a profound impact on their replication and expression. The chromosomes of higher eukaryotes possess discrete compartments that are characterized by differing transcriptional activities. Contrastingly, most bacterial chromosomes have simpler organization with local domains, the boundaries of which are influenced by gene expression. Numerous studies have revealed that the higher-order architectures of bacterial and eukaryotic chromosomes are dependent on the actions of structural maintenance of chromosomes (SMC) superfamily protein complexes, in particular, the nearuniversal condensin complex. Intriguingly, however, many archaea, including members of the genus Sulfolobus do not encode canonical condensin. We describe chromosome conformation capture experiments on Sulfolobus species. These reveal the presence of distinct domains along Sulfolobus chromosomes that undergo discrete and specific higherorder interactions, thus defining two compartment types. We observe causal linkages between compartment identity, gene expression, and binding of a hitherto uncharacterized SMC superfamily protein that we term ''coalescin.''
It has been postulated that a myriad of long noncoding RNAs (lncRNAs) contribute to gene regulation. In fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1). At the fbp1 promoter, this transcription promotes chromatin remodeling and fbp1 mRNA expression. Here, we demonstrate that such upstream noncoding transcription facilitates promoter association of the stress-responsive transcriptional activator Atf1 at the sites of transcription, leading to activation of the downstream stress genes. Genome-wide analyses revealed that ∼50 Atf1-binding sites show marked decrease in Atf1 occupancy when cells are treated with a transcription inhibitor. Most of these transcription-enhanced Atf1-binding sites are associated with stress-dependent induction of the adjacent mRNAs or lncRNAs, as observed in fbp1. These Atf1-binding sites exhibit low Atf1 occupancy and high histone density in glucose-rich conditions, and undergo dramatic changes in chromatin status after glucose depletion: enhanced Atf1 binding, histone eviction, and histone H3 acetylation. We also found that upstream transcripts bind to the Groucho-Tup1 type transcriptional corepressors Tup11 and Tup12, and locally antagonize their repressive functions on Atf1 binding. These results reveal a new mechanism in which upstream noncoding transcription locally magnifies the specific activation of stress-inducible genes via counteraction of corepressors.
Shortage of glucose, the primary energy source for all organisms, is one of the most critical stresses influencing cell viability. Glucose starvation promptly induces changes in mRNA and noncoding RNA (ncRNA) transcription. We previously reported that glucose starvation induces long ncRNA (lncRNA) transcription in the 5 0 segment of a fission yeast gluconeogenesis gene (fbp1 + ), which leads to stepwise chromatin alteration around the fbp1 + promoter and to subsequent robust gene activation. Here, we analyzed genomewide transcription by strandspecific RNA sequencing, together with chromatin landscape by immunoprecipitation sequencing (ChIP-seq). Clustering analysis showed that distinct mRNAs and ncRNAs are induced at the early, middle and later stages of cellular response to glucose starvation. The starvation-induced transcription depends substantially on the stress-responsive transcription factor Atf1. Using a new computer program that examines dynamic changes in expression patterns, we identified ncRNAs with similar behavior to the fbp1 + lncRNA. We confirmed that there are continuous lncRNAs associated with local reduction of histone density. Overlapping with the regions for transcription of these lncRNAs, antisense RNAs are antagonistically transcribed under glucose-rich conditions. These results suggest that Atf1-dependent integrated networks of mRNA and lncRNA govern drastic changes in cell physiology in response to glucose starvation.
The Tup family corepressors contribute to critical cellular responses, such as the stress response and differentiation, presumably by inducing repressive chromatin, though the precise repression mechanism remains to be elucidated. E ukaryotic chromosomal DNA is packaged in a highly organized and condensed chromatin structure. Many DNA-associated reactions, including DNA damage repair, replication, recombination, and transcription, are regulated by the chromatin structure (1, 2). The chromatin structure is modulated by two distinct classes of regulators, histone modification enzymes and ATP-dependent chromatin remodeling factors (3, 4). Such regulatory components are recruited by two types of cis-acting regulatory factors, transcriptional activators and repressors. Transcriptional activators and repressors bind to cis-acting elements to activate and repress transcription, respectively, by affecting the chromatin structure and regulating RNA polymerase II accumulation in the promoter region (5-7). These transcriptional regulators also interact with coactivators and corepressors to regulate gene expression (8, 9). The Tup family transcriptional corepressors are conserved between yeast and humans and regulate gene expression during the stress response and cellular differentiation (10, 11). Saccharomyces cerevisiae Tup1 represses some genes regulated by cell type, glucose, oxidative stress, DNA damage, and other cellular stress responses (12, 13). Tup1 represses the expression of genes via distinct mechanisms: by establishing a repressive chromatin structure around the target gene promoter, by recruiting histone deacetylases, and by directly interfering with the general transcription machinery (14-18). Two Tup1 orthologs in Schizosaccharomyces pombe, Tup11 and Tup12 (Tup11/12), regulate multiple stress-responsive genes, including the fbp1 ϩ and cta3 ϩ genes, to provide stress specificity (19,20). However, the precise molecular mechanisms of Tup1 family proteins in gene repression have not been fully uncovered.The fbp1 ϩ gene encodes fructose-1,6-bisphosphatase and is robustly induced upon glucose starvation (21,22). fbp1 ϩ expression is strictly repressed by Tup11/12 and activated by the transcriptional activators Atf1, Rst2, and Php5 (23-26). Atf1, a bZIP protein, is regulated through phosphorylation by the mitogen-activated protein kinase pathway (27-29), while Rst2, a C 2 H 2 Zn finger-type protein, is under the regulation of the protein kinase A pathway (23, 30). Php5, a component of the S. pombe CCAATbinding factor (CBF; also known as NF-Y) that possesses a histone hold domain, forms a complex with Php2/Php3 and contributes to cyc1 ϩ transcription (31, 32). In addition, two cis-acting elements required for fbp1 ϩ transcription have been identified (33). Upstream activation sequence 1 (UAS1) contains a cyclic AMP response element (CRE) and is the binding site for Atf1 and its binding partner, Pcr1 (34), while UAS2 resembles the S. cerevisiae stress response element (STRE) and serves as the binding site for Rst2 (...
Eukaryotic cells produce a variety of non-coding RNAs (ncRNAs), many of which have been shown to play pivotal roles in biological processes such as differentiation, maintenance of pluripotency of stem cells, and cellular response to various stresses. Genome-wide analyses have revealed that many ncRNAs are transcribed around regulatory DNA elements located proximal or distal to gene promoters, but their biological functions are largely unknown. Recently, it has been demonstrated in yeast and mouse that ncRNA transcription around gene promoters and enhancers facilitates DNA binding of transcription factors to their target sites. These results suggest universal roles of promoter/enhancer-associated ncRNAs in the recruitment of transcription factors to their binding sites.
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