PL1003 Lecture 3.6: Transcription Factors and Steroid Hormones - PDF

Transcription Factors and Steroid Hormones Dr. Gemma Barron [email protected] This Photo by Unknown Author is licensed under CC BY-SA Today’s Learning Outcomes At the end of today’s class, you should be able to: Explore fundamental concepts in cellular biology...

Transcription Factors and Steroid Hormones Dr. Gemma Barron [email protected] This Photo by Unknown Author is licensed under CC BY-SA Today’s Learning Outcomes At the end of today’s class, you should be able to: Explore fundamental concepts in cellular biology and pharmacology: Describe what transcription factors are (i.e., basal transcription machinery and altering the rate of This Photo by Unknown Author is licensed under CC BY-SA transcription) and why they are important to the cell. Define and explain steroid hormones recognising their function and role in biological systems. Why is this important? Mechanisms of drug action Personalised medicine and pharmacogenetics Managing side effects and drug interactions Treatment of hormone-related disorders Drug development and pharmacological research Transcription Factors Diseases in eukaryotes… Cancers Autoimmune disorders Metabolic conditions … This Photo by Unknown Author is licensed under CC BY Transcription factors Transcription factors (TFs) are proteins that bind to specific DNA sequences and regulate / control transcription. ·Basal transcription machinery ·Attaches to promoter, and helps RNA polymerase to attach ·Unwinds the DNA to initiate transcription ·TFs that alter rate of transcription ·Turn transcription up / down or on / off in response to biological or environmental factors https://www.khanacademy.org/science/ap-biology/gene-expression-and-regulation/regulation-of-gene- 18 expression-and-cell-specialization/a/eukaryotic-transcription-factors The transcriptional complex Basal transcriptional machinery Transcription proceeds at an exceedingly low rate Enhanced by ‘transcription factors’  DNA Binding Domain (DBD) Region of TF which binds directly to specific DNA sequences. Often called ‘promoters’ or ‘enhancers’ which determine if genes will be activated Key or repressed. Transactivation Domains characteristi Region of TF which interacts with other proteins involved in gene expression. Helps to initiate transcription. cs of Regulatory Function transcriptio Activators (increasing transcription) Repressor (decreasing transcription) n factors Important in maintaining balance within cells and responding to external signals, e.g., hormones. Promotors and Enhancers Promoter Upstream of the coding sequence of the gene Specific motif; NOT transcribed TATA box with consensus 5’-TATAAA-3’ Basal transcription factors bind to the TATA box, recruiting RNA polymerase Enhancer Region Short section of DNA found up to 1,000,000 bp up- or down-stream of the gene Binds to transcription factors, altering rate of transcription Different enhancers are specific to different transcription factors What else? Inducible Not all genes have response elements for all transcription. Account for different appearance and function of cells. Silencers and repressor transcription factors. Regulation Transcription factors Many genes are controlled by several different transcription factors, with a specific combination needed to turn the gene on = combinatorial regulation https://www.khanacademy.org/science/ap biology/gene expression and regulation/regulation of gene expression-and-cell-specialization/a/eukaryotic-transcription-factors Steroid Hormones Steroid hormones Class of lipophilic molecules derived from cholesterol. Easily pass through the cell membrane and bind to specific receptors inside the cell. Divided into three categories based on function: Sex steroids (e.g., oestrogen, testosterone) Glucocorticoids (e.g., cortisol) Mineralocorticoids (e.g., aldosterone) Binding to intracellular receptors How do steroid hormones work? This Photo by Unknown Author is licensed under CC BY-NC Steroid hormones Not stored in vesicles Production can be stepped up rapidly, but still takes time Ligands for transcription factors (SHR) Alter gene expression Therefore, response measured in hours to days How to think about this... What effects do steroid hormones have on their target tissues? What question are we really asking? Which genes are switched on by steroid hormone receptors? An example... aldosterone Osmolarity: amount of solute per unit volume Drives water movement if it can! This is important in the kidney Sodium Control sodium movement......water movement will follow Functional unit of kidney: The nephron What does aldosterone do to the body? That last sodium transporter is aldosterone-sensitive Acts on the kidney to enhance Na+ retention Therefore enhances water retention Increases blood volume (and pressure) Increases pressure driving formation of tissue fluid Renin-angiotensin-aldosterone system The detail: Gene targets Two-step process: First is passive (Na conc in the lumen is very high) Facilitated by ENaC Second is active Driven by Na+/K+-ATPase Both are gene targets of aldosterone Response elements present in the promoter An example... Oestrogen and testosterone Key in reproductive health Hormone replacement therapy (HRT) Synthetic versions of these hormones Post – menopausal symptoms or hormone deficiencies. This Photo by Unknown Author is licensed under CC BY Summary You need to be able to describe what transcription factors are and why they are important to the cell. You also need to be able to define and explain steroid hormones recognising their function and role in biological systems. Ideas for further reading and discussion will be uploaded to the PL1003 Moodle page.