Written Assignment for Unit 2 CHEM 3212 Biochemistry University of the People Instructor: Anupriya Chatterjee 11/29/23
Introduction The perception that genetic predisposition solely determines disease risk has long prevailed in society. Commonly, individuals attribute their susceptibility to ailments like heart disease or cancer to family history, emphasizing the role of genes in health outcomes. Yet, this view oversimplifies the complex interplay between genetics and disease. While genetic alterations contribute to some illnesses, a substantial portion of disease occurrences stem from epigenetic factors, influencing gene expression independent of DNA code changes. Understanding nucleosome remodeling sheds light on the intricate mechanisms governing gene expression. Histones, crucial proteins around which DNA coils to form nucleosomes, undergo modifications that profoundly impact gene regulation. This essay explores the chemistry of histone-DNA interactions, three key histone modifications affecting gene activation, and their implications in the Central Dogma. Furthermore, it delves into a disease or physiological disorder and investigates the epigenetic pathways associated with its development. Nucleosome Formation and Histone-DNA Interaction: The assembly of nucleosomes involves histones, specifically histone proteins H2A, H2B, H3, and H4, around which DNA strands wrap. Histones consist of globular domains and flexible tails that interact with DNA. Positively charged amino acids within histones (lysine, arginine) attract negatively charged DNA through electrostatic interactions, forming nucleosomes (Ettig et al., 2011). Histone Modifications Influencing Gene Activation: 1. Acetylation: Acetyl groups (COCH3) are added to histone lysine residues, neutralizing their positive charge. This neutralization reduces the histone-DNA affinity, loosening
chromatin structure, and promoting gene activation. Acetylation generally enhances transcriptional activity (How Do Histone Modifications Regulate Gene Expression?, 2023). 2. Methylation: Methyl groups (CH3) are attached to histone lysine or arginine residues. Depending on the specific site and number of methyl groups, methylation can either activate or repress gene transcription. For instance, methylation at certain lysine positions of histone H3 (e.g., H3K4me3) is associated with active gene transcription (How Do Histone Modifications Regulate Gene Expression?, 2023). 3. Phosphorylation: Addition of phosphate groups (PO4) to histone serine or threonine residues can regulate chromatin structure. Phosphorylation often correlates with increased transcriptional activity by loosening chromatin structure and facilitating access for transcription factors (How Do Histone Modifications Regulate Gene Expression?, 2023). Implications in the Central Dogma: These histone modifications influence gene expression by altering chromatin structure, thus impacting the transcription of DNA into mRNA. Epigenetic changes mediated by nucleosome remodeling can modulate the accessibility of DNA to transcription factors, thereby regulating gene expression in the transcriptional phase of the Central Dogma (What Is the 'Central Dogma'?, n.d .- b). Disease or Physiological Disorder and Epigenetic Mechanisms: Cancer as a Case Study Cancer exemplifies a complex disease involving multifaceted interactions between genetic and epigenetic factors. Research suggests that aberrant histone modifications contribute to cancer development. For instance, altered histone acetylation or methylation patterns at