Chromatin and the Human Genome

Flashcards testing core concepts on DNA structure, histones, chromatin compaction, gene regulation, repetitive elements, and epigenetics from Dr. Jonathan Lerner's lecture.

What is the definition of a human genome?

The complete set of genetic material in an organism.

What does it mean that human somatic cells are diploid ($2n$)?

They contain two copies of each chromosome: $22$ pairs of autosomal chromosomes plus sex-specific chromosomes ($XX$ or $XY$).

Who discovered and published the double helix structure of DNA in Nature in 1953?

James Watson and Francis Crick, along with contributions from Rosalind Franklin and Maurice Wilkins.

What three distinct chemical interactions stabilize the DNA double helix?

1. Hydrogen bonds between complementary nitrogenous bases
2. Phosphodiester bonds along the sugar-phosphate backbone
3. Hydrophobic interactions (base stacking) between adjacent bases

How many hydrogen bonds form between Adenine-Thymine ($A\text{-}T$) and Guanine-Cytosine ($G\text{-}C$) base pairs?

$2$ hydrogen bonds between $A\text{-}T$ pairs and $3$ hydrogen bonds between $G\text{-}C$ pairs.

By standard biological convention, in what direction is a DNA sequence written and read?

From the $5'$ end to the $3'$ end ($5'$ to $3'$).

Why does the DNA backbone possess an overall negative charge?

Due to the negatively charged phosphate groups ($PO_4^{3-}$) linking the deoxyribose sugars.

What is the physical physical length of a single base pair, and what is the total physical length of the diploid human genome?

One base pair measures $340崇pm$ (3.4 \times 10^{-10崇m), and the total diploid genome measures approximately $6'5$ (6.5 feet).

Which four core histone proteins assemble to form a histone octamer?

Two copies each of $H2A$, $H2B$, $H3$, and $H4$.

How many base pairs of DNA wrap around a single histone octamer to form a nucleosome core?

$143崇bp$ of DNA.

What is the minimal degree of chromatin compaction, often referred to as "beads on a string"?

The $11崇nm$ fiber.

How does chromatin compaction differ between interphase and mitosis?

Interphase chromosomes have a lower, highly heterogeneous compaction level, whereas mitotic chromosomes reach the maximum level of compaction ($1/10000$).

What three specialized chromosomal functional regions are required for proper chromosome maintenance and propagation?

1. Telomeres (chromosome ends)
2. Centromeres (central region for mitotic handles)
3. Origins of replication (sites of DNA synthesis)

What specific repetitive DNA sequence makes up human telomeres, and what is its primary role?

$(TTAGGG)_n$ repeats; they protect chromosome ends against degradation and illegal end-joining.

Approximately how many origins of replication exist across the human genome?

$30,000\text{--}50,000$ origins of replication.

What is a karyotype, and what is its primary clinical purpose?

The microscopic visualization of an individual's complete set of chromosomes, used to detect large chromosomal structural or numerical abnormalities.

Approximately how many protein-coding genes are present in the human genome?

Approximately $30,000$ protein-coding genes.

What are the core structural features of a typical human protein-coding gene?

Exons (protein-encoding sequences), introns (noncoding intervening sequences), untranslated regions ($5'$ UTR and $3'$ UTR), and a promoter.

How can a single protein-coding gene produce multiple distinct protein isoforms?

Through alternative splicing of pre-mRNA, which selectively includes or excludes different exons.

How do non-coding RNA genes differ structurally from protein-coding genes?

Non-coding RNA genes (e.g., rRNA, tRNA, miRNA) lack exons and introns because the RNA transcript itself directly performs the biological function without being translated into protein.

How do promoters and enhancers differ in location and regulatory function?

Promoters are located immediately upstream of genes and bind general transcription factors to recruit RNA Polymerase II for basal transcription. Enhancers are located at a distance and bind specific transcription factors to greatly increase transcription levels via Mediator complex interactions.

What percentage of the human genome consists of repetitive DNA sequences?

Approximately $50崇$ of the human genome.

What molecular genetic mutation is responsible for Huntington disease?

An abnormal expansion of a $CAG$ microsatellite repeat within the coding sequence of the Huntingtin gene, which codes for glutamine.

What are the structural differences between LINEs and SINEs in the human genome?

LINEs (Long Interspersed Nuclear Elements) are $\text{~}7000崇bp$ long and repeated $20,000\text{--}50,000$ times. SINEs (Short Interspersed Nuclear Elements) are $90\text{--}500崇bp$ long and repeated $\text{~}100,000$ times.

What is the biological definition of epigenetics?

Heritable changes in cell function or gene expression that do not involve modifications of the underlying DNA sequence.

How do euchromatin and heterochromatin differ in structural compaction and transcriptional activity?

Euchromatin is loosely packed, accessible to transcription factors, and transcriptionally active. Heterochromatin is densely packed, inaccessible, and transcriptionally repressed.

How does histone acetylation affect chromatin architecture and gene expression?

Histone Acetyl Transferase (HAT) adds acetyl groups ($-COCH_3$) to lysine tails, neutralizing positive charges and weakening histone-DNA interactions to decondense chromatin and activate transcription. Histone Deacetylase (HDAC) removes them to compact chromatin.

How do the histone tail modifications $H3K4me3$ and $H3K9me3$ differ in their effect on gene expression?

$H3K4me3$ recruits proteins that open chromatin (producing active euchromatin), whereas $H3K9me3$ recruits proteins that compact chromatin (producing repressed heterochromatin).

On what specific base sequence motif does human DNA methylation primarily occur?

On Cytosine nucleotides directly preceding a Guanine nucleotide ($CpG$ dinucleotides).

What are CpG islands, and where are they usually found?

Genomic regions rich in unmethylated $CpG$ dinucleotides (approximately $20,000$ in the human genome), typically located upstream of or inside gene promoters.

How does the protein MeCP2 promote gene silencing at methylated CpG sites?

$MeCP2$ selectively binds methylated $CpGs$ and recruits co-repressors like Histone Deacetylases (HDACs) and $mSIN3A$ to compact chromatin.

What molecular mechanism underlies Rett Syndrome?

De novo mutations in the $MeCP2$ gene cause loss of function, leading to impaired gene silencing during neuronal development and pathological gene overexpression.

What molecular mechanism causes Fragile X Syndrome?

Expansion of a $CGG$ trinucleotide repeat in the $5'$ UTR of the $FMR1$ gene on the X chromosome to over $200$ repeats (normal is $5\text{--}44$), causing hypermethylation of the region and silencing of $FMR1$ transcription.