Molecular Biology: Chromatin Structure and Function

DNA wraps around histone proteins forming a structure resembling beads on a string. This structure is 11nm in diameter and is the first level of DNA compaction.

The "beads on a string" structure, also known as the 11nm fiber, is further compacted by coiling into a solenoid structure. This structure is 30nm in diameter and represents the second level of DNA compaction.

Histone modifications like acetylation and methylation regulate DNA accessibility and gene expression. Acetylation is often associated with active transcription, while methylation can be associated with either active or repressed transcription.

Histone acetylation makes chromatin more accessible, allowing for greater transcription.

The 30nm chromatin fiber is further packaged into loops attached to a protein scaffold called SAR (Scaffold Attachment Regions) or MAR (Matrix Attachment Regions). This results in a 300nm fiber, the third level of DNA compaction.

The 300nm fiber condenses into a 600-700nm fiber, also known as a chromatid. This is the final level of DNA packaging before cell division. During mitosis, DNA reaches its most condensed state, 10,000 times more compact than the initial 2nm fiber.

The dynamic nature of histone modifications allows for alterations in DNA accessibility, regulating processes like replication and gene expression.

The level of DNA packaging can change depending on the cell's needs, with euchromatin being more loosely packed and accessible for gene expression, while heterochromatin remains tightly packed and less accessible.

The DNA molecule opens at specific points called origins of replication where replication begins.

Initiator proteins recognize specific nucleotide sequences at the origin of replication.

The initiator proteins facilitate the attachment of other proteins that separate the two DNA strands, creating two replication forks.

A group of enzymes and proteins called the replisome is involved in the molecular mechanism of replication.

The replisome works differently in prokaryotes and eukaryotes.

In prokaryotes, there is a single origin of replication, and the replication forks move in opposite directions along the circular chromosome.

In eukaryotes, multiple origins of replication are needed to replicate the long chromosomes in a reasonable time.

The E.coli genome replicates from a single origin in 30 minutes while mammalian genomes would take about 3 weeks if they replicated from a single origin.

A type of RNA that binds to a protein complex called RISC and targets complementary mRNAs, leading to either translation inhibition or mRNA degradation. Each miRNA can target multiple mRNAs (up to 100) and plays a role in various cellular processes like development and regulation of cell growth.

A non-coding RNA molecule larger than 200 nucleotides that participates in regulating gene expression primarily in eukaryotes. There are thousands of long non-coding RNAs discovered in humans.

A complex structure embedded in the nuclear envelope that serves as the gatekeeper for molecules traveling between the nucleus and cytoplasm. It controls the exchange of molecules in both directions, allowing selective transport.

A double-layered membrane surrounding the nucleus. It serves as a barrier between the nucleus and the cytoplasm, controlling the flow of molecules between the two compartments.

The inner layer of the nuclear envelope that provides structural support to the nucleus and serves as an attachment point for chromatin.

A fibrous network located beneath the inner nuclear membrane (INM) that provides structural support for the nucleus and helps organize chromatin.

Tandem repeats of short DNA sequences (1-500 nucleotides) that occur thousands of times in genomes. They do not code for proteins and are not actively transcribed, but they are important for chromosome structure.

A type of repetitive DNA sequence that appears as separate bands (satellites) in density gradient centrifugation because of its AT-rich composition. It's less dense than other genomic DNA regions.

Enzymes that unwind the DNA double helix during replication, using energy from ATP hydrolysis.

Proteins that bind to single-stranded DNA after it's unwound by helicases. They prevent the strands from re-associating and keep them ready for copying.

Enzymes that relieve the stress caused by the unwinding of DNA during replication, by temporarily breaking and then rejoining the DNA strands.

The replication fork is formed when the double helix is unwound and separated. It's where DNA synthesis occurs: Two DNA polymerase molecules, primase, and a helicase work together for leading and lagging strand DNA synthesis.

DNA polymerase is incredibly accurate, copying DNA with very few errors. It achieves this partly by selecting the correct base, although the exact mechanism is still being researched.

DNA polymerase has a 'proofreading' ability. It can remove incorrectly added bases, working in the opposite direction of DNA synthesis. This helps to ensure even greater replication accuracy.

Telomerase is a specialized DNA polymerase that adds repetitive sequences to the ends of chromosomes (telomeres). This prevents chromosome shortening during replication.

Telomerase is special because it's only capable of synthesizing oligonucleotide sequences that are specific to telomeres. This helps to maintain chromosome integrity.

Sequences in DNA located far from the transcription start site that bind transcription factors to regulate gene expression.

Promoter sequences that bind specific transcription factors and initiate gene expression.

The ability of enhancers to regulate gene expression regardless of their distance or orientation from the transcription start site is due to the formation of loops in DNA.

Enhancers often have multiple binding sites for different regulatory proteins, working together to fine-tune gene expression.

Enhancers are involved in various cellular processes like development, differentiation, and responses to hormones and growth factors.

Enhancers constitute a substantial portion of human genomic DNA, emphasizing their importance in regulating gene expression.

Mutations affecting enhancers can disrupt gene expression and contribute to various diseases.

The immunoglobulin heavy-chain enhancer has multiple binding sites, demonstrating the complexity of gene regulation.

The process of creating ribosomes, essential for protein synthesis, involves the transcription and processing of ribosomal RNA (rRNA) molecules.

The nucleolus, a distinct region within the nucleus, is the site of ribosome assembly. It contains the genes for rRNA and is highly active in transcription and processing.

The 5.8S, 18S, and 28S rRNAs are transcribed as a single unit, initially forming a 45S pre-rRNA, before being processed into their individual forms.

The human genome contains multiple copies of the genes encoding rRNA, ensuring sufficient rRNA production to meet the cell's demands for ribosome synthesis.

The nucleolus is organized around specific regions of chromosomes containing the genes for 5.8S, 18S, and 28S rRNAs, called nucleolar organization regions (NORs).

The nucleolus can vary in size depending on the cell's metabolic activity, with larger nucleoli indicating higher protein synthesis.

The three distinct regions of the nucleolus – FC, DFC, and G – represent different stages of rRNA processing and ribosome assembly.

The 45S pre-rRNA undergoes a series of cleavages to produce mature 18S, 5.8S, and 28S rRNA molecules, eventually leading to the formation of ribosomal subunits.