The proteasome is a multi-subunit machine that unfolds and degrades proteins. How is its activity regulated such that it only degrades certain proteins?

When challenged with a low oxygen environment, known as hypoxia, the body produces a hormone called erythropoietin (EPO), which then stimulates red blood cell production to carry more oxygen. Transcription of the gene encoding EPO is dependent upon the hypoxia-inducible factor (HIF), which is a transcriptional activator. However, HIF alone is not sufficient to activate EPO. For example, Wang et al. (2010. PLOS ONE 5: e10002) showed that HIF recruits another protein called p300 to an enhancer for the EPO gene. Furthermore, deletion of p300 significantly impaired transcription of the EPO gene in response to hypoxia. Given that p300 is a type of histone acetyl transferase, how might p300 influence transcription of the EPO gene?

The TBX20 transcription factor is important for the development of heart tissue. Deletion of the Tbx20 gene in mice results in poor heart development and the death of mice well before birth. To better understand how TBX20 regulates heart development at a genetic level, Sakabe et al. (2012. Hum. Mol. Genet. 21:2194–2204) performed a transcriptome analysis in which they compared the levels of all mRNAs between heart cells from wild-type mice and mice with Tbx20 deleted.

How might such a transcriptome analysis provide information about how TBX20 regulates heart development?

The TBX20 transcription factor is important for the development of heart tissue. Deletion of the Tbx20 gene in mice results in poor heart development and the death of mice well before birth. To better understand how TBX20 regulates heart development at a genetic level, Sakabe et al. (2012. Hum. Mol. Genet. 21:2194–2204) performed a transcriptome analysis in which they compared the levels of all mRNAs between heart cells from wild-type mice and mice with Tbx20 deleted.

This study concluded that TBX20 acts as an activator of some genes but a repressor of other genes in cardiac tissue. How might a single transcription factor have opposite effects on the transcription of different genes?

Many viruses that infect eukaryotic cells express genes that alter the regulation of host gene expression to promote viral replication. For example, herpes simplex virus-1 (HSV-1) expresses a protein called ICP0, which is necessary for successful viral infection and replication within the host. Lutz et al. (2017. Viruses 9: 210) showed that ICP0 can act as a ubiquitin ligase and target the redundant transcriptional repressors ZEB1 and ZEB2, which leads to upregulation of the miR-183 cluster (a set of three miRNAs transcribed from the same locus).

What likely happens to ZEB1 and ZEB2 upon HSV-1 infection?

Many viruses that infect eukaryotic cells express genes that alter the regulation of host gene expression to promote viral replication. For example, herpes simplex virus-1 (HSV-1) expresses a protein called ICP0, which is necessary for successful viral infection and replication within the host. Lutz et al. (2017. Viruses 9: 210) showed that ICP0 can act as a ubiquitin ligase and target the redundant transcriptional repressors ZEB1 and ZEB2, which leads to upregulation of the miR-183 cluster (a set of three miRNAs transcribed from the same locus).

How may ICP0 expression in a host cell lead to upregulation of the miR-183 cluster?

Many viruses that infect eukaryotic cells express genes that alter the regulation of host gene expression to promote viral replication. For example, herpes simplex virus-1 (HSV-1) expresses a protein called ICP0, which is necessary for successful viral infection and replication within the host. Lutz et al. (2017. Viruses 9: 210) showed that ICP0 can act as a ubiquitin ligase and target the redundant transcriptional repressors ZEB1 and ZEB2, which leads to upregulation of the miR-183 cluster (a set of three miRNAs transcribed from the same locus).

Speculate on how miR-183 cluster upregulation may benefit the virus.