Chromatin Structure and Gene Transcription

Altering Chromatin Structures

• Three main processes alter gene transcription: histone modification, chromatin remodeling, and DNA methylation.

Histones

• Nucleosomes consist of an octamer of histone proteins around which 147 base pairs of DNA are coiled.
• Core histones include H2A, H2B, H3, and H4, with H1 acting as a linker protein.

Histone Code

• The histone code is a pattern of post-translational modifications that influencing chromatin state and gene expression.
• Modifications like acetylation, methylation, phosphorylation, and ubiquitination impact functionality and are heritable epigenetic marks.

Active and Repressive Marks

• Active marks facilitate gene expression, while repressive marks silence gene activity.
• The specific covalent modifications depend on the amino acid composition of histone tails.

Histone Acetylation

• Acetylation neutralizes the positive charge of lysine, reducing histone affinity for DNA, allowing for transcriptional activation.
• Histone Acetyltransferases (HAT) add acetyl groups; Histone Deacetylases (HDAC) remove them.
• Hyperacetylation occurs near actively expressed genes.

DNA Methylation

• Methylation, especially within CpG islands, is a well-understood form of epigenetic regulation leading to gene repression.
• 5-methylcytosine (5mC) is the result of methylation, promoting chromatin condensation and blocking transcription factor binding.
• Approximately 1.5% of human DNA is 5mC, significant given that about 2% encodes proteins.

DNA Methyltransferases (DNMTs)

• DNMT1 maintains existing methylation patterns during DNA replication, while DNMT3a and 3b establish new methylation patterns.
• Hemimethylated DNA aids in identifying which strand should be methylated post-replication.

DNA Demethylation

• The removal of methyl groups reverses methylation effects, crucial for epigenetic reprogramming.
• TET proteins (TET1, TET2, TET3) catalyze this process, enhancing transcriptional activation.

Hypomethylation and Hypermethylation

• Hypomethylation results in more active transcription, promoting growth but increasing chromosomal instability.
• Hypermethylation silences genes involved in regulating cell growth, DNA repair, and apoptosis.

Epigenetic Inheritance

• Epigenetic tags can be inherited without changes to the DNA sequence itself, allowing parental experiences to affect offspring.
• Epigenetic alterations may be erased in a zygote but can still be passed down.

Identical Twins and Epigenetics

• Comparisons of DNA methylation patterns in twins show that similar patterns exist in youth, but diverge in older age, demonstrating the influence of environment on epigenetics.

Environmental Impact on Development

• Genetic identicality in bees shows that environmental factors, such as diet (e.g., royal jelly), affect the expression of genes related to worker and queen development through DNA methylation.