A comparative analysis of divergently-paired genes (DPGs) among Drosophila and vertebrate genomes

Yang, Liang; Yu, Jun

doi:10.1186/1471-2148-9-55

Cited by 33 publications

(36 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tip60/NuA4 binds to the cycB promoter and 59 intron, suggesting that cycB could be directly regulated by NuA4 (Filion et al 2010). Interestingly, cycB is located in the genome as a divergently paired gene (DPG) (Yang and Yu 2009) with stall, which is upregulated 6.5-fold upon Tip60 inhibition. Tip60/NuA4 may therefore act to direct the proper transcription of certain DPGs with differential expression patterns.…”

Section: Discussionmentioning

confidence: 99%

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

Flegel¹,

Grushko²,

Bolin³

et al. 2016

Genetics

View full text Add to dashboard Cite

Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo. However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed Drosophila, Rbf, E2F and Myb/Multi-vulva class B (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression.KEYWORDS DNA damage; proliferation; H2Av; cell cycle checkpoint; cell cycle exit A conserved eukaryotic transcriptional oscillator controls cell cycle gene expression in proliferating cells and underlies the well-studied Cyclin/Cdk cell cycle protein oscillator (Orlando et al. 2008;Oikonomou and Cross 2010). In metazoans, this oscillator depends upon transcriptional activation of several hundred cell cycle genes, initiated by E2F transcription factor complexes followed by E2F inhibition (or degradation) (Shibutani et al. 2008;Zielke et al. 2011;Sadasivam and Decaprio 2013). This generates an oscillation of chromatin opening and closing at cell cycle genes that is thought to properly coordinate G1/S and G2/M gene expression as well as the transition to a noncycling state (Litovchick et al. 2007(Litovchick et al. , 2011Forristal et al. 2014). Disruption of this coordination can affect cell cycle progression by causing inappropriate gene expression (Reis and Edgar 2004;Wen et al. 2008;Forristal et al. 2014). While the oscillation of E2F activity is required for robust cell cycle gene expression Korenjak et al. 2012), E2F complexes are not absolutely essential for cell cycle progression or timely cell cycle exit in Drosophila (Frolov et al. 2001(Frolov et al. , 2005. In the absence of E2F activity there must be E2F-independ...

show abstract

Section: Discussionmentioning

confidence: 99%

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

Flegel¹,

Grushko²,

Bolin³

et al. 2016

Genetics

View full text Add to dashboard Cite

show abstract

“…If coexpression of close head-to-head gene pairs provides lower fitness, selection should favor rearrangements that result in physical or functional separation of the two genes. A comparative analysis of head-to-head gene pairs in different species revealed that these pairs are more conserved in vertebrate lineage than in Drosophila species (Yang and Yu 2009;Weber and Hurst 2011). Drosophila has more close head-to-head gene pairs than mammals, but the conservation of these pairs is threefold lower (Yang and Yu 2009).…”

Section: Discussionmentioning

confidence: 99%

“…A comparative analysis of head-to-head gene pairs in different species revealed that these pairs are more conserved in vertebrate lineage than in Drosophila species (Yang and Yu 2009;Weber and Hurst 2011). Drosophila has more close head-to-head gene pairs than mammals, but the conservation of these pairs is threefold lower (Yang and Yu 2009). This suggests that some of the head-to-head gene pairs in Drosophila arise from genome compaction rather than selection for this specific organization.…”

Section: Discussionmentioning

confidence: 99%

“…Approximately 10% of genes in vertebrates are arranged in a head-to-head orientation and located closer than 1 kb from each other (Adachi and Lieber 2002;Yang et al 2008). The proportion of close head-to-head gene pairs in the genome correlates with gene density (Li et al 2006;Yang and Yu 2009), and Drosophila shows a higher than expected proportion of genes in this type of arrangement (Koyanagi et al 2005;Yang and Yu 2009). The intergenic regions of close head-to-head gene pairs are referred to as bidirectional promoters, indicating that the two TSS's are close enough to share the same upstream regulatory region (Adachi and Lieber 2002;Koyanagi et al 2005).…”

mentioning

confidence: 99%

“…The intergenic regions of close head-to-head gene pairs are referred to as bidirectional promoters, indicating that the two TSS's are close enough to share the same upstream regulatory region (Adachi and Lieber 2002;Koyanagi et al 2005). Genes positioned in a head-tohead orientation show overall higher correlation of expression than those arranged in other orientations Yang and Yu 2009). However, there are also head-to-head gene pairs whose expression is not correlated or is negatively correlated in both humans and Drosophila Li et al 2006).…”

mentioning

confidence: 99%

See 2 more Smart Citations

The BEAF-32 insulator coordinates genome organization and function during the evolution of Drosophila species

2012

View full text Add to dashboard Cite

Understanding the relationship between genome organization and expression is central to understanding genome function. Closely apposed genes in a head-to-head orientation share the same upstream region and are likely to be coregulated. Here we identify the Drosophila BEAF-32 insulator as a cis regulatory element separating close head-to-head genes with different transcription regulation modes. We then compare the binding landscapes of the BEAF-32 insulator protein in four different Drosophila genomes and highlight the evolutionarily conserved presence of this protein between close adjacent genes. We find that changes in binding of BEAF-32 to sites in the genome of different Drosophila species correlate with alterations in genome organization caused by DNA rearrangements or genome size expansion. The cross-talk between BEAF-32 genomic distribution and genome organization contributes to new gene-expression profiles, which in turn translate into specific and distinct phenotypes. The results suggest a mechanism for the establishment of differences in transcription patterns during evolution.

show abstract

Bidirectional Gene Pairs in the Human Genome

Koyanagi

Imanishi

Gojobori

2013

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Bidirectional gene pairs, also called head‐to‐head gene pairs, are defined as two genes on different strands with adjacent 5′‐ends. They are transcribed divergently in a variety of coordinated fashion. The region between a bidirectional gene pair is designated as a putative bidirectional promoter, which is suggested to coordinately regulate the expression of the pair. The closely located bidirectional gene pairs and their bidirectional promoters were recently found to be enriched in the human genome. Despite substantial interests in these gene pairs and their expression regulation through bidirectional promoters, their biological significance is not well understood. Furthermore, it is of particular interest to know when and how the bidirectional gene arrangement evolved. Here the current understanding of these pairs is reviewed: bidirectional gene pairs may have great biological significance, and the bidirectional gene arrangement has evolved during the evolution of vertebrates leading to mammals by relocation of existing genes. Key Concepts: Closely located bidirectional gene pairs are enriched in the human genome. Bidirectional gene pairs show correlated expression pattern. Bidirectional gene pairs tend to have basic function in cells such as DNA repair. Bidirectional promoters lack TATA boxes and are enriched in CpG islands. Specific transcription factors are overrepresented in bidirectional promoters. Bidirectional genes pairs tend to transcribe actively. Bidirectional gene arrangement has evolved during the evolution of vertebrates leading to mammals by relocation of existing genes. Detailed mechanisms of bidirectional transcription and the evolutionary forces that shaped the bidirectional arrangement in the human genome remain to be elucidated.

show abstract

A comparative analysis of divergently-paired genes (DPGs) among Drosophila and vertebrate genomes

Cited by 33 publications

References 65 publications

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

The BEAF-32 insulator coordinates genome organization and function during the evolution of Drosophila species

Bidirectional Gene Pairs in the Human Genome

Contact Info

Product

Resources

About