DNA, Chromatin, and the Nucleus

100 Q&A flashcards covering nucleus, chromatin structure, epigenetics, nuclear envelope, lamina, nuclear pore complex, and nucleolus.

What is chromatin?

DNA and protein complex that packages DNA in the nucleus.

How long is DNA in one human nucleus?

Approximately 2 meters.

What is the approximate diameter of the largest nuclei mentioned?

About 10 μm.

What packaging challenge must chromatin solve?

Pack DNA ~10^4‑fold while allowing orderly replication and transcription.

What is euchromatin?

A lightly packed form of chromatin enriched in genes and often transcriptionally active.

Where is heterochromatin typically located and why?

At the nuclear periphery, attached to the nuclear lamina, and less accessible for transcription.

What is the first level of chromatin structure called?

The nucleosome (10 nm fiber).

What does a nucleosome consist of?

Approximately 200 bp of DNA wrapped around an octamer of histone proteins.

What is bead in the beads-on-a-string description?

An octamer of histone proteins around which DNA is wrapped.

Which histone families form the core particle?

H2A, H2B, H3, and H4.

What is the role of histone H1?

Linker histone between nucleosomes.

What are histone modifications used for?

Regulate chromatin structure and transcription; can be rapid and reversible.

How is acetylation achieved on histones?

By histone acetyltransferases (HATs).

What is the effect of histone acetylation on transcription?

Activation of transcription by neutralizing histone charges.

What is the effect of histone deacetylation?

Repression of transcription by removing acetyl groups.

What is histone methylation and its consequence?

Methylation of histone H3 by HMTs promotes heterochromatin formation via HP1 and represses transcription.

Where do histone modifications occur?

On the amino-terminal tails of core histones.

What are epigenetic modifications?

Heritable changes in gene function without changes in DNA sequence (includes DNA methylation and histone modifications).

What enzyme adds DNA methylation?

DNA methyltransferases (DNMTs).

What is the effect of DNA methylation on transcription?

Repression by blocking transcription factor binding.

How are epigenetics connected to cancer therapy?

Epigenetic changes can repress tumor suppressor genes; therapies target DNMTs, HDACs, and HMTs.

Name a DNMT inhibitor used in therapy.

5-azacytidine (Vidaza).

Name a commonly used HDAC inhibitor.

Vorinostat (and Panobinostat).

Name an HMT inhibitor mentioned.

Tazverik.

Do transcribing chromatin lack H1? If so, what is the promoter feature?

Yes; no H1 and 1–2 nucleosomes may be absent from a gene’s promoter.

What is the 2nd order of chromatin structure called?

The 30-nanometer fiber (solenoid).

How many nucleosomes per turn in the 30-nm fiber?

Six nucleosomes per turn.

What is required to form the 30-nm fiber?

Histone H1.

What are the 3rd and 4th orders of chromatin structure?

Loops and minibands.

What is a miniband?

A wrap of 30-nm fibers containing ~18 loops and ~1,000,000 bp of DNA.

How many loops are in a miniband?

About 18 loops.

What is the 5th order of chromatin structure?

The chromosome.

Approximately how many base pairs are in a chromosome?

About 75 million base pairs.

How is chromatin condensed into chromosomes?

Hyper-phosphorylation of chromatin proteins.

What is the centromere?

Locus of repetitive DNA in the middle of the chromosome; anchor points for chromosome separation during cell division.

What are telomeres?

GGGTTA repeats at chromosome ends that protect and stabilize ends.

What happens to telomeres after each cell division?

Some telomere is lost after each cell division.

What maintains telomere length in germline and some cancers?

Telomerase.

Are cancer cells immortal?

Some cancers are immortal due to telomerase activation.

What are the two membranes of the nuclear envelope?

Outer membrane and inner membrane.

What does the outer membrane of the nuclear envelope harbor?

Ribosomes/ER.

What does the inner membrane harbor?

The nuclear lamina and marginal heterochromatin.

What is the nuclear pore complex?

Thousands per nucleus; contains nucleoporins forming 3 octameric rings that transport proteins and RNA.

What are nucleoporins?

Members of the 30-member nucleoporin family.

What is the function of the nuclear pore complex?

Bind to and transport proteins (>65 kD) and RNA across the nuclear envelope.

What is the nuclear lamina?

Structure between the inner nuclear envelope and marginal heterochromatin.

What proteins compose the lamina?

Lamins A, B, and C.

How does lamin B connect to the inner nuclear envelope?

Lamin B binds the Lamin B Receptor (LBR).

How do lamins A and C interact with chromatin?

They bind marginal heterochromatin.

What is the function of the nuclear lamina during the cell cycle?

During interphase, it helps maintain nucleus shape; during mitosis lamins A/C are hyper-phosphorylated leading to breakdown, while lamin B stays bound to LBR to aid re-formation.

What are laminopathies?

Diseases caused by LMNA mutations, including muscular dystrophy, cardiomyopathy, and premature aging (progeria).

What genes encode lamins A/C and B?

LMNA encodes lamins A/C; LMNB encodes lamins B.

What is the function of the nucleolus?

A ribosome factory; transcribes rRNA and assembles ribosomal subunits.

What is NOR?

Nucleolar organizer region; region on 10 chromosomes that contains rRNA genes.

How many rRNA genes are on each NOR chromosome?

40 rRNA genes per chromosome.

How many rRNA genes are there in total in NORs?

400 (10 chromosomes x 40 genes each).

Which enzyme transcribes rRNA in the nucleolus?

RNA polymerase I.

What binds to rRNA transcripts inside the nucleolus?

Ribonucleoproteins (RNPs).

Where are the 40S and 60S ribosomal subunits formed?

In the nucleus.

Where do ribosomal subunits mature into mature ribosomes?

In the cytoplasm after export through nuclear pores.

What is the final ribosome form in the cytoplasm?

80S ribosome.

What is the basic unit of chromatin structure?

Nucleosome.

Which histones form the core octamer?

H2A, H2B, H3, and H4.

Which histone is the linker between beads?

Histone H1.

Where do histone modifications occur?

On the amino-terminal tails of core histones.

What recruits histone modifying enzymes?

Transcription activator and repressor proteins.

How do histone modifications impact transcription?

By altering electrostatic charge and providing binding sites for transcription regulatory proteins.

What is HP1 and its role?

Heterochromatin Protein 1; binds methylated H3 and promotes heterochromatin formation and repression.

What is epigenetics?

Heritable changes in gene function without a DNA sequence change.

What is DNA methylation?

Addition of methyl groups to CpG cytosine residues by DNMTs.

What is the effect of DNA methylation on transcription factor binding?

Blocks binding and represses gene expression.

What is the clinical relevance of epigenetic modifications in cancer?

Methylation and histone modifications can repress tumor suppressor genes; drugs target these pathways.

What are the clinical examples of epigenetic drugs?

DNMT inhibitors (e.g., 5-azacytidine), HDAC inhibitors (e.g., Vorinostat), HMT inhibitors (e.g., Tazverik).