Epigenetic Regulation and Gene Expression Inheritance FINAL EXAM CONTENT PDF

Epigenetic Regulation and Gene Expression Inheritance Key Concepts: 1. Gene Expression Patterns: ○ Gene expression is regulated primarily during interphase. ○ Most transcription and synthesis processes cease during mitosis, meaning gene regulatory mechanisms are typically...

Epigenetic Regulation and Gene Expression Inheritance Key Concepts: 1. Gene Expression Patterns: ○ Gene expression is regulated primarily during interphase. ○ Most transcription and synthesis processes cease during mitosis, meaning gene regulatory mechanisms are typically reset after cell division. ○ However, some mechanisms ensure stable inheritance of gene expression patterns even without changes to DNA sequences. 2. Epigenetic Regulation: ○ Epigenetics refers to heritable changes in gene expression without altering the DNA sequence. ○ Essential for cellular differentiation: E.g., Liver cells divide into liver cells without "relearning" their identity. Stem cells can differentiate into various specialized cell types like red blood cells or fat cells. Four Mechanisms of Epigenetic Regulation: 1. Positive Feedback Loops: ○ A protein (e.g., Protein A) activates its own transcription after being initially induced. ○ Even after the initial signal is removed, the protein maintains its expression. ○ Ensures stable gene expression until a new signal interrupts the loop. 2. Covalent Histone Modifications: ○ Histones can be chemically modified (e.g., acetylation, methylation), altering chromatin accessibility and gene expression. ○ During DNA replication, histone codes are replicated to ensure daughter cells inherit the same gene expression patterns. ○ Histone modification ensures regions of the genome remain active or silenced across cell generations.  3. DNA Methylation: ○ Methyl groups are added to CpG sequences on DNA, silencing genes. ○ Maintenance methyltransferase ensures methylation patterns are preserved after DNA replication. Newly synthesized DNA strands are initially unmethylated. The enzyme methylates the new strand to match the template strand, maintaining silencing patterns across cell divisions. 4. Protein Aggregates (e.g., Prions): ○ Proteins can adopt alternative folding states that propagate themselves. ○ Pathological examples: Prion diseases: Misfolded proteins influence others to misfold. Alzheimer’s and Parkinson’s diseases: Protein aggregates maintain their pathological states, even through cell divisions. ○ While often pathological, this represents a stable epigenetic change. Epigenetic Regulation and Cellular Differentiation: Epigenetic Memory: Allows cells to retain specialized functions across divisions. Stable Changes: Epigenetic mechanisms ensure that specific gene expression patterns are passed down in multicellular organisms, facilitating tissue and organ function. QUESTION: Which of the following is an example of epigenetic regulation? a. A transcription factor regulating its own expression in a positive feedback loop b. A kinase cascade activating a transcription factor c. Binding of a steroid hormoneot its receptor inducing nuclear localization d. microRNA-mediated downregulation of a messenger RNA e. Al of the above Positive Feedback Loop of a Transcription Factor:  Epigenetic regulation often involves the stable and heritable control of gene expression. A transcription factor that regulates its own expression through a positive feedback loop can establish a self-sustaining expression state. This type of regulation can lead to persistent activation or repression of a gene, even after the initial signal has ceased. This mechanism is considered epigenetic because it involves changes to gene expression that persist across cell divisions without altering the underlying DNA sequence. Lecture Notes for Exam Preparation: Cellular Transport and Topological Compartments 1. Key Transport Mechanisms in Cells Cytoplasmic to Nuclear Transport (Topologically Similar Compartments) ○ Molecules exit the nucleus and enter the cytosol. ○ Transport occurs between areas that are topologically similar (e.g., cytosol and nucleus). ○ This type of transport involves gates (e.g., nuclear pore complexes). Transmembrane Transport (Topologically Different Compartments) ○ Movement across membranes between the cytosol and organelles like the ER, mitochondria, or chloroplasts. ○ Typically unidirectional: proteins are synthesized in the cytosol and transported into organelles. ○ Mechanisms involve protein translocators that aid movement across the membranes. Vesicular Transport (Intra-Organelle and Bidirectional) ○ Movement between organelles such as ER to Golgi, Golgi to plasma membrane, or Golgi back to ER. ○ Involves vesicles that shuttle cargo while maintaining the topology of membrane orientation. 2. Topological Similarities and Differences  Definition of Topological Similarity: Compartments sharing the same internal or external membrane orientation. Example: ○ Nucleus and cytosol are topologically similar. ○ ER lumen and extracellular space are topologically equivalent. Differences in Membrane Composition: ○ Organelles have unique lipid compositions (e.g., sphingolipids or phospholipids in varying proportions). ○ This impacts the functional specificity of organelles. Membrane Orientation: ○ When a membrane is synthesized in the ER, its orientation is preserved during transport. ○ The cytosolic-facing leaflet of the membrane in the ER will remain cytosolic-facing in the final destination. 3. Sorting and Transport of Proteins  Challenges of Protein Transport: ○ Proteins must cross or embed into membranes while retaining proper orientation. ○ Mechanisms address whether proteins stay on the same side or cross to the opposite side of the membrane. Sorting Signals: ○ Proteins carry intrinsic "addresses" (sorting signals) that guide their destination. ○ Types of Sorting Signals: Signal Peptides: Short sequences directing proteins to specific compartments. Signal Patches: Formed by the 3D folding of the protein, recognized by sorting machinery. Role of Sorting Receptors: ○ Sorting receptors recognize and bind to sorting signals. ○ Function to segregate and deliver proteins to their designated compartments. ○ Examples include receptors for internal signals and signal patches. 4. Transport Pathways and Their Regulation Vesicular Transport Examples: ○ ER → Golgi → Plasma Membrane → Extracellular Space (secretory pathway). ○ Golgi → ER (retrieval pathway). ○ Bidirectional vesicular transport ensures balance in protein and membrane flow. Mechanisms in Signal Recognition and Sorting: ○ Sorting receptors ensure specificity by binding unique signal sequences. ○ Proteins without appropriate signals remain in their default compartment. Lecture Notes: Cellular Transport Mechanisms and Protein Sorting 1. Introduction to Protein Transport  Cells rely on highly organized mechanisms to transport proteins to their correct locations, ensuring proper cellular function. Transport mechanisms fall into three categories based on the topology (spatial relationship) of compartments involved: 1. Gated Transport (e.g., between the cytosol and nucleus). 2. Transmembrane Transport (e.g., between the cytosol and organelles like the ER or mitochondria). 3. Vesicular Transport (e.g., between organelles such as the ER and Golgi). 2. Gated Transport: Nuclear-Cytosol Exchange Topological Similarity: ○ The nucleus and cytosol are topologically similar due to the continuity of the nuclear envelope and ER membrane. ○ This means their compartments are "on the same side" of the membrane system, despite selective transport requirements. The Nuclear Pore Complex (NPC): ○ Functions as a selective gate allowing macromolecules to move in and out of the nucleus. ○ Small molecules (