Understanding Chromosome Organization and Gene Regulation

Chromosome Territories (CTs)

Distinct, non-overlapping domains in the nucleus occupied by individual chromosomes

Chromosome Distribution in the Nucleus

Nonrandom; gene-rich chromosomes (e.g. Chr19) are more central, gene-poor (e.g. Chr18) more peripheral

Main Chromatin States

Euchromatin (open, active) and Heterochromatin (closed, inactive)

Topologically-Associated Domains (TADs)

Chromatin regions that self-interact to regulate genes in localized neighborhoods

NADs and LADs

Nucleolar- and Lamina-Associated Domains; nuclear compartments linked to gene repression

A and B Compartments in Chromatin

A = active regions; B = repressed regions

Chromatin State Determinants

Histone modifications (acetylation/methylation) of histone tails

Histone Acetylation

Opens chromatin (activates transcription)

Histone Methylation

Often closes chromatin (represses transcription)

Histone Modifying Enzymes

HATs (acetylate), HMTs (methylate), with corresponding deacetylases and demethylases

Telomeres

Protective caps at chromosome ends

Centromeres

Regions that link sister chromatids during mitosis

Promoters and Enhancers

Cis-elements that activate transcription of nearby genes

Silencers and Insulators

Silencers repress transcription; insulators block regulatory element interference

Gene

A DNA segment that codes for a functional product (RNA or protein)

Cis-acting Elements

Non-coding sequences that regulate nearby genes (not transcribed)

Trans-acting Elements

Transcribed sequences (like RNAs) that regulate distant targets

Protein Coding in Human Genome

Only ~1.5%, around 30,000 protein-coding genes

Function of tRNA

Transfers amino acids during protein synthesis; found in cytoplasm and mitochondria

Function of rRNA

Forms part of ribosomes; essential for protein synthesis and ribozyme activity

Long Non-coding RNAs (lncRNAs)

>200 nt RNAs involved in gene regulation and chromatin interaction

Small Non-coding RNAs

<200 nt RNAs like miRNAs that regulate gene expression post-transcriptionally

Importance of Non-coding Regions

They regulate gene expression, structure chromatin, and affect genome evolution

ENCODE Project

Encyclopedia of DNA Elements; maps coding and non-coding functional genomic elements

Exome Sequences Limitations

They miss regulatory (non-coding) regions, which also cause disease

Genome Composition Beyond Genes

Repetitive regions, intergenic regions, transposons, pseudogenes, regulatory sequences

Transposons

Mobile DNA elements that can move within the genome; mutagenic and evolutionarily important