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Transcriptional and Post-transcriptional Regulation of Gene Expression
Title
Transcriptional and Post-transcriptional Regulation of Gene Expression.
Creator
Ding, Jun, Hu, Haiyan, Li, Xiaoman, Zhang, Shaojie, Jin, Yier, University of Central Florida
Abstract / Description
Regulation of gene expression includes a variety of mechanisms to increase or decrease specific gene products. Gene expression can be regulated at any stage from transcription to post-transcription and it's essential to almost all living organisms, as it increases the versatility and adaptability by allowing the cell to express the needed proteins. In this dissertation, we comprehensively studied the gene regulation from both transcriptional and post-transcriptional points of view....
Show moreRegulation of gene expression includes a variety of mechanisms to increase or decrease specific gene products. Gene expression can be regulated at any stage from transcription to post-transcription and it's essential to almost all living organisms, as it increases the versatility and adaptability by allowing the cell to express the needed proteins. In this dissertation, we comprehensively studied the gene regulation from both transcriptional and post-transcriptional points of view. Transcriptional regulation is by which cells regulate the transcription from DNA to RNA, thereby directing gene activity. Transcriptional factors (TFs) play a very important role in transcriptional regulation and they are proteins that bind to specific DNA sequences (regulatory elements) to regulate the gene expression. Current studies on TF binding are still very limited and thus, it leaves much to be improved on understanding the TF binding mechanism. To fill this gap, we proposed a variety of computational methods for predicting TF binding elements, which have been proved to be more efficient and accurate compared with other existing tools such as DREME and RSAT peaks-motif. On the other hand, studying only the transcriptional gene regulation is not enough for a comprehensive understanding. Therefore, we also studied the gene regulation at the post-transcriptional level. MicroRNAs (miRNAs) are believed to post-transcriptionally regulate the expression of thousands of target mRNAs, yet the miRNA binding mechanism is still not well understood. In this dissertation, we explored both the traditional and novel features of miRNA-binding and proposed several computational models for miRNA target prediction. The developed tools outperformed the traditional microRNA target prediction methods (.e.g miRanda and TargetScan) in terms of prediction accuracy (precision, recall) and time efficiency.
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Date Issued
2016
Identifier
CFE0006098, ucf:51197
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0006098
STUDIES ON A NOVEL HUMAN CARDIOSPECIFIC TRANSCRIPTION FACTOR AND ITS INVOLVEMENT IN OMI/HTRA2 MEDIATED CELL DEATH
Title
STUDIES ON A NOVEL HUMAN CARDIOSPECIFIC TRANSCRIPTION FACTOR AND ITS INVOLVEMENT IN OMI/HTRA2 MEDIATED CELL DEATH.
Creator
Puthucode Balakrishnan, Meenakshi, Zervos, Antonis, University of Central Florida
Abstract / Description
Omi/HtrA2 is a mitochondrial serine protease that is known to translocate to the cytoplasm upon induction of apoptosis and to activate caspase-dependent and caspase-independent cell death. The molecular mechanism of Omi/HtrA2ÂÂ's function is not clear but involves degradation of specific substrates. These substrates include cytoplasmic, mitochondrial, as well as nuclear proteins. We have isolated a new Omi/HtrA2 interactor, the THAP5 protein. THAP5 is a fifth member of...
Show moreOmi/HtrA2 is a mitochondrial serine protease that is known to translocate to the cytoplasm upon induction of apoptosis and to activate caspase-dependent and caspase-independent cell death. The molecular mechanism of Omi/HtrA2ÂÂ's function is not clear but involves degradation of specific substrates. These substrates include cytoplasmic, mitochondrial, as well as nuclear proteins. We have isolated a new Omi/HtrA2 interactor, the THAP5 protein. THAP5 is a fifth member of a large family of transcription factors that are involved in cell proliferation, apoptosis, cell cycle control, chromosome segregation, chromatin modification and transcriptional regulation. THAP5 is an approximately 50kDa nuclear protein, with a restricted pattern of expression. Furthermore, there is no mouse or rat homolog for this protein. THAP5 mRNA is highly expressed in the human heart but some expression is also seen in the brain and skeletal muscle. The normal function of THAP5 in the heart or heart disease is unknown. THAP5 protein level is significantly reduced in the myocardial infarction (MI) area in the heart of patients with coronary artery disease (CAD). This part of the heart sustains most of the cellular damage and apoptosis. Our data clearly show that THAP5 is a specific substrate of the proapoptotic Omi/HtrA2 protease and is cleaved and removed during cell death. The molecular mechanism of THAP5ÂÂ's function is unclear. THAP5 can bind to a specific DNA sequence and repress transcription of a reporter gene. Our work suggests that THAP5 is a tissue specific transcriptional repressor that plays an important role in the normal function of the human heart as well as in the development of heart disease.
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Date Issued
2010
Identifier
CFE0003412, ucf:48409
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0003412