Human Genetics: Chromatin Insights

Human Genetics

• Human Genetics is a study of the medical laboratory techniques in the 3rd stage at Al-Salam University College, Baghdad, Iraq.

Chromatin

• Chromatin is a complex of DNA and protein found in eukaryotic cells.
• Its primary function is to package long DNA molecules into compact, denser structures to prevent tangling.
• It also plays roles in DNA reinforcement, damage prevention, gene expression regulation, and DNA replication.
• During mitosis and meiosis, chromatin facilitates proper chromosome segregation in anaphase.
• The characteristic chromosome shapes visible during this stage result from DNA coiling into highly condensed chromatin.
• Total cellular DNA is about 5-6 feet long and needs to fit inside the nucleus.
• DNA first wraps around histone proteins, forming nucleosomes.
• Nucleosomes coil and condense to form chromatin fibers.
• Chromatin fibers unwind for DNA replication and transcription.
• During cell replication, duplicated chromatins condense into visible chromosomes that are separated into daughter cells.

Chromatin Structure and Cell Cycle

• Overall chromatin network structure depends on the stage of the cell cycle.
• During interphase, chromatin is structurally loose to allow RNA and DNA polymerases access for DNA transcription and replication.
• Local chromatin structure during interphase depends on the specific genes present in DNA.
• Regions with active genes (euchromatin) are less tightly compacted and associated with RNA polymerases, while regions with inactive genes (heterochromatin) are more condensed and associated with structural proteins.
• Epigenetic modifications (methylation and acetylation) of structural proteins in chromatin also alter local chromatin structure and gene expression.

Types of Chromatin

• Euchromatin: A lightly packed form of chromatin enriched in genes and usually under active transcription. It is mostly under active transcription.
• Heterochromatin: A tightly packed form of chromatin that is less accessible for transcription. It is associated with inactive genes. Multiple varieties exist.
• Constitutive heterochromatin: Found throughout chromosomes in eukaryotes, located at pericentromeric regions and telomeres. It has a structural function and composed of satellite DNA. It influences gene expression via position-effect variegation (PEV).
• Facultative heterochromatin: Composed of euchromatin that takes on staining and compactness characteristics of heterochromatin during development. The inactive X-chromosome is made up of facultative heterochromatin.

Functions of Chromatin

• Chromatin plays significant roles in gene regulation and chromosome protection. Its dense packaging makes DNA less accessible to proteins that usually bind to it.
• This packaging can protect DNA from damage and regulate gene expression.
• This packaging is tightly packed, it was thought to be inaccessible to polymerases, thus not able to be transcribed. However, much of this DNA is in fact transcribed, but it is continually turned over via RNA-induced transcriptional silencing.

DNA Packaging

• DNA is packaged into chromatin so protein production can be controlled.
• DNA forms a double helix.
• Phosphate groups in DNA give it a negative charge, counteracted by histone proteins which package the DNA.
• Millions of nucleosomes tightly coil the continuous DNA strand into chromatin, further condensed into the chromosome during cell division.
• DNA replication and transcription access is dependent on the chromatin state(euchromatin or heterochromatin).
• Replication occurs at origins of replication throughout the DNA strand to accelerate replication and transcribe and replicate DNA.
• Interactions between DNA and histone proteins, mediated by post-translational modifications (methylation, acetylation), dictate the active or inactive state of genes.
• Methylation typically suppresses gene expression, while acetylation increases accessibility and expression.