Genetics and Evolution - Molecular Basis of Inheritance - Nucleosome

Slide 1

• Introduction to Molecular Basis of Inheritance - Nucleosome
• Definition of Nucleosome
• Role of Nucleosome in DNA packaging and organization
• Importance of Nucleosome in gene expression regulation
• Overview of the topics covered in the lecture

Slide 2

• Structure and Composition of Nucleosome
• Core histones (H2A, H2B, H3, H4) and linker histone (H1)
• DNA wrapping around the histone octamer
• Linker DNA and its role in nucleosome structure
• Demonstration of nucleosome structure through a diagram

Slide 3

• DNA Packaging and Nucleosome Formation
• DNA compaction at multiple levels - from nucleosome to chromosome
• Role of histones in stabilizing DNA structure
• Electrostatic interactions between histones and DNA
• Nucleosome assembly and disassembly

Slide 4

• Functions of Nucleosome
• Protection of DNA from damage
• Facilitating DNA replication and repair
• Control of gene transcription and DNA accessibility
• Importance of nucleosome positioning in gene regulation
• Examples of nucleosome functions in various biological processes

Slide 5

• Nucleosome Dynamics and Modifications
• Histone modifications like acetylation, methylation, phosphorylation, etc.
• Role of histone modifications in gene regulation and chromatin remodeling
• Chromatin accessibility and nucleosome remodeling complexes
• Impact of nucleosome modifications on DNA packaging and gene expression

Slide 6

• DNA Methylation and Nucleosome Structure
• DNA methylation patterns in different cell types
• Role of DNA methylation in gene silencing
• Interplay between DNA methylation and nucleosome structure
• Epigenetic inheritance and nucleosome modifications

Slide 7

• Nucleosome Positioning and Gene Regulation
• Role of nucleosome positioning in transcriptional control
• Nucleosome occupancy and DNA accessibility
• Transcription factors and nucleosome remodeling complexes
• Influence of nucleosome positioning on gene expression levels

Slide 8

• Molecular Techniques to Study Nucleosomes
• Chromatin immunoprecipitation (ChIP)
• DNase I footprinting assay
• Micrococcal nuclease digestion assay
• High-throughput sequencing approaches for nucleosome mapping

Slide 9

• Nucleosome and Disease Associations
• Aberrant nucleosome structure in cancer cells
• Role of nucleosomes in epigenetic diseases
• Nucleosome modifications as potential therapeutic targets
• Examples of diseases associated with nucleosome dysregulation

Slide 10

• Summary of Key Points
• Nucleosome as the fundamental unit of DNA packaging
• Role of nucleosome in gene regulation and DNA accessibility
• Impact of nucleosome dynamics and modifications on cellular processes
• Techniques used to study nucleosome structure and function
• Association between nucleosomes and human diseases

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Slide 11

• Regulation of Gene Expression by Nucleosomes
  • Nucleosome positioning influences access to DNA by transcription factors
  • Transcriptional activators can recruit chromatin remodeling complexes to alter nucleosome positions
  • Enhancers and promoters have unique nucleosome occupancy patterns
  • Nucleosome modifications can modulate transcriptional activity

Slide 12

• Chromatin Remodeling Complexes
  • ATP-dependent chromatin remodeling complexes can slide, evict or replace nucleosomes
  • SWI/SNF family of remodeling complexes
  • ISWI family of remodeling complexes
  • INO80 family of remodeling complexes

Slide 13

• Nucleosome Mapping Techniques
  • Chromatin immunoprecipitation followed by sequencing (ChIP-seq)
  • Micrococcal nuclease (MNase) digestion followed by sequencing (MNase-seq)
  • Assay for Transposase Accessible Chromatin using sequencing (ATAC-seq)
  • Formaldehyde-Assisted Identification of Regulatory Elements (FAIRE-seq)

Slide 14

• Role of Nucleosomes in DNA Replication
  • Nucleosome disassembly during replication initiation
  • Histone chaperones aid in assembly of newly synthesized histones onto DNA
  • Nucleosome reassembly after replication
  • Epigenetic inheritance of nucleosome modifications during replication

Slide 15

• Nucleosome Positioning and Transcriptional Regulation
  • Nucleosome-free regions (NFRs) are typically found near transcription start sites
  • Nucleosome occupancy can be influenced by transcription factors and chromatin modifiers
  • Nucleosome positioning can impact promoter accessibility and transcriptional efficiency

Slide 16

• Nucleosome Modifications and Gene Regulation
  • Histone acetylation promotes gene expression by loosening nucleosome-DNA interactions
  • Histone methylation can either activate or repress gene expression, depending on specific residues and context
  • Histone phosphorylation plays a role in transcriptional regulation and DNA damage repair
  • Crosstalk between different histone modifications coordinates gene expression patterns

Slide 17

• Histone Variants and Nucleosome Functions
  • Histone variants have specialized roles in specific chromatin regions
  • Examples: H2A.Z, H3.3, and MacroH2A
  • Variant histones can influence nucleosome stability, positioning, and gene regulation

Slide 18

• Nucleosomes and X-Chromosome Inactivation
  • X-chromosome inactivation is a process by which one X chromosome is inactivated in female cells
  • Xist RNA recruits proteins that induce heterochromatin formation and nucleosome remodeling
  • Nucleosome modifications play a role in the silencing of genes on the inactivated X chromosome

Slide 19

• Nucleosome Dynamics in Aging and Disease
  • Age-related changes in nucleosome positioning and modifications
  • Links between nucleosome dynamics and neurodegenerative diseases
  • Nucleosome alterations in cancer and their potential as biomarkers
  • Targeting nucleosome modifications for therapeutic purposes

Slide 20

• Recap and Key Concepts
  • Nucleosomes play a critical role in DNA packaging, gene regulation, and epigenetic inheritance
  • Nucleosome positioning and modifications influence gene expression and accessibility
  • Chromatin remodeling complexes regulate nucleosome dynamics
  • Various techniques are used to study nucleosome structure and function
  • Nucleosome dysregulation is associated with disease and aging

Slide 21

• Nucleosome Variability and Gene Expression
  • Nucleosome occupancy patterns can vary between different cell types and organisms
  • Differences in nucleosome positioning can regulate tissue-specific gene expression
  • Examples of nucleosome positioning in development and differentiation
  • Structural variations in nucleosome composition and their impact on gene regulation

Slide 22

• Nucleosome Modifications and Epigenetic Memory
  • Histone modifications can be maintained through cell divisions and inherited by daughter cells
  • Role of histone modifications in establishing and maintaining cellular identity
  • Epigenetic memory and its importance in development and disease
  • Environmental influences on nucleosome modifications and epigenetic memory

Slide 23

• Nucleosome Dynamics and Transcriptional Pausing
  • Nucleosome occupancy and positioning influence RNA Pol II transcription
  • Nucleosomes can cause transcriptional pausing and regulate gene expression levels
  • Nucleosome modifications can impact RNA Pol II elongation
  • Examples of genes regulated by nucleosome dynamics and transcriptional pausing

Slide 24

• Nucleosomes and Chromatin States
  • Chromatin has distinct states: open (euchromatin) and compact (heterochromatin)
  • Nucleosomes play a role in establishing and maintaining chromatin states
  • Chromatin states and their impact on gene accessibility and transcriptional regulation
  • Interplay between nucleosome modifications, chromatin states, and gene expression

Slide 25

• Nucleosome Repositioning and DNA Repair
  • Nucleosome repositioning is necessary for efficient DNA repair
  • Nucleosome remodeling complexes aid in nucleosome displacement during repair
  • Role of nucleosome positioning in repair pathway choice (e.g., homologous recombination vs. non-homologous end joining)
  • Impact of nucleosome modifications on DNA repair efficiency

Slide 26

• Nucleosome Structure and Epigenetics
  • Epigenetics refers to heritable changes in gene expression without changes in DNA sequence
  • Nucleosome structure and modifications are key components of epigenetic regulation
  • Nucleosomes can act as carriers of epigenetic information
  • Examples of epigenetic phenomena involving nucleosomes (e.g., genomic imprinting, paramutation)

Slide 27

• Nucleosomes and Genome Organization
  • Nucleosome positioning contributes to higher-order genome organization
  • Chromosome territories and nuclear compartments
  • Interactions between nucleosomes, histones, and nuclear structures
  • Role of nucleosomes in spatial genome organization

Slide 28

• Nucleosomes and Developmental Processes
  • Nucleosome dynamics and modifications play critical roles in development
  • Activation and repression of lineage-specific genes during differentiation
  • Role of nucleosomes in embryonic development and tissue morphogenesis
  • Transgenerational effects of nucleosome modifications on development

Slide 29

• Nucleosomes and Genetic Disorders
  • Mutations in nucleosome-associated proteins can lead to genetic disorders
  • Examples: histone variants, histone-modifying enzymes, chromatin remodelers
  • Dysregulation of nucleosome structure and modifications in disease contexts
  • Therapeutic strategies targeting nucleosome dynamics in genetic disorders

Slide 30

• Recap and Summary
  • Nucleosomes are the basic units of DNA packaging and organization in the nucleus
  • Nucleosome positioning and modifications play crucial roles in gene regulation and chromatin structure
  • Nucleosome dynamics and modifications are influenced by various factors, including transcription, replication, and environmental cues
  • Dysregulation of nucleosome structure and function can contribute to diseases, including cancer and genetic disorders
  • Future research directions in the field of nucleosome biology