A large-scale cancer-specific protein-DNA interaction network.

Cancer development and progression are generally associated with gene dysregulation, often resulting from changes in the transcription factor (TF) sequence or expression. Identifying key TFs involved in cancer gene regulation provides a framework for potential new therapeutics. This study presents a large-scale cancer gene TF-DNA interaction network, as well as an extensive promoter clone resource for future studies. Highly connected TFs bind to promoters of genes associated with either good or poor cancer prognosis, suggesting that strategies aimed at shifting gene expression balance between these two prognostic groups may be inherently complex. However, we identified potential for oncogene-targeted therapeutics, with half of the tested oncogenes being potentially repressed by influencing specific activators or bifunctional TFs. Finally, we investigate the role of intrinsically disordered regions within the key cancer-related TF ESR1 in DNA binding and transcriptional activity, and found that these regions can have complex trade-offs in TF function. Altogether, our study broadens our knowledge of the TFs involved in cancer gene regulation and provides a valuable resource for future studies and therapeutics.

A large-scale cancer-specific protein-DNA interaction network.

Cancer development and progression are generally associated with dysregulation of gene expression, often resulting from changes in transcription factor (TF) sequence or expression. Identifying key TFs involved in cancer gene regulation provides a framework for potential new therapeutics. This study presents a large-scale cancer gene TF-DNA interaction network as well as an extensive promoter clone resource for future studies. Most highly connected TFs do not show a preference for binding to promoters of genes associated with either good or poor cancer prognosis, suggesting that emerging strategies aimed at shifting gene expression balance between these two prognostic groups may be inherently complex. However, we identified potential for oncogene targeted therapeutics, with half of the tested oncogenes being potentially repressed by influencing specific activator or bifunctional TFs. Finally, we investigate the role of intrinsically disordered regions within the key cancer-related TF estrogen receptor ɑ (ESR1) on DNA binding and transcriptional activity, and found that these regions can have complex trade-offs in TF function. Altogether, our study not only broadens our knowledge of TFs involved in the cancer gene regulatory network but also provides a valuable resource for future studies, laying a foundation for potential therapeutic strategies targeting TFs in cancer.

Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors.

Cooperativity and antagonism between transcription factors (TFs) can drastically modify their binding to regulatory DNA elements. While mapping these relationships between TFs is important for understanding their context-specific functions, existing approaches either rely on DNA binding motif predictions, interrogate one TF at a time, or study individual TFs in parallel. Here, we introduce paired yeast one-hybrid (pY1H) assays to detect cooperativity and antagonism across hundreds of TF-pairs at DNA regions of interest. We provide evidence that a wide variety of TFs are subject to modulation by other TFs in a DNA region-specific manner. We also demonstrate that TF-TF relationships are often affected by alternative isoform usage and identify cooperativity and antagonism between human TFs and viral proteins from human papillomaviruses, Epstein-Barr virus, and other viruses. Altogether, pY1H assays provide a broadly applicable framework to study how different functional relationships affect protein occupancy at regulatory DNA regions.

Effect of Neural Tissue Mobilization on Sensory-Motor Impairments in Breast Cancer Survivors with Lymphedema: An Experimental Study.

BACKGROUND: Breast surgery, Axillary Lymph Node Dissection (ALND), radiation and chemotherapy may develop several complications such as axillary web syndrome, frozen shoulder, numbness, shoulder pain and range of motion restriction, lymphostasis, and lymphedema. Up to 77% report sensory disturbance in the breast or arm after breast surgery. These short- and long-term consequences have dramatic impact on physical function and quality of life in this population. AIMS: The aim of the study was to determine the effect of neural tissue mobilization on sensory-motor impairments in breast cancer survivors with lymphedema. SUBJECTS AND METHODS: This study was carried out by analyzing total 100 breast cancer survivor women, with lymphedema aged between 30-65 years of age who had undergone breast surgery mostly lumpectomy along with chemotherapy or radiation therapy. Participants were divided into two groups by random allocation. One group underwent neurodynamic mobilization and the other group conventional physiotherapy.The treatment protocol was given for 6 weeks. Parameters such ROM, pain, lymphedema and sensory-motor impairments were assessed at the baseline before the treatment and 6 weeks after the treatment. RESULT: The result from this study shows that there is significant improvement (p<0.0001, t-value 4.69) in mTNS of patients undergoing neural tissue mobilization,whereas there was no significant improvement (p=0.05, t-value 1.951) seen in patients undergoing conventional physiotherapy. CONCLUSION: This study concludes that effect of neural tissue mobilization has significant impact on sensory motor impairments as compared to conventional treatment protocol in breast cancer survivors with lymphedema.Pain and ROM showed similar difference with both the treatment protocols. It was also observed that patients with mild and moderate lymphedema showed significant improvement as compared to patients with severe lymphedema.