Genetics 380 Lecture 12: Chromosome Structure and Epigenetics

Vocabulary flashcards covering the structural hierarchy of DNA packaging, chromatin differentiation, histone modifications, DNA methylation, X-inactivation, and genomic imprinting.

Loop Domains

The first level of DNA packaging in prokaryotes, in which loops of genomic DNA are held in place by DNA-binding proteins.

Supercoiling

A level of prokaryotic DNA packaging that occurs within loop domains, where DNA rotations are added or removed to over- or under-wind the helix.

Topoisomerases

Enzymes that add or remove helical rotations from DNA, mediating the transition between relaxed and supercoiled DNA states.

Chromatin

The eukaryotic complex consisting of genomic DNA bound to proteins.

Chromosome

A structure formed from chromatin that is highly condensed, reaching its maximum compaction at metaphase ($1400\,\text{nm}$).

Heterochromatin

A form of chromatin that remains highly condensed and tightly packed throughout the entire cell cycle, characterized by an absence of gene expression.

Euchromatin

Chromatin whose level of packaging changes dynamically during the cell cycle and which contains actively expressed genes.

Constitutive Heterochromatin

Chromatin regions that remain permanently condensed and transcriptionally inactive throughout the cell cycle in all cells, such as centromeres and telomeres.

Facultative Heterochromatin

Chromatin that is condensed and silenced only at specific developmental stages or in specific cell lineages, such as the mammalian inactive X chromosome.

Centromere

A heterochromatic chromosomal region to which spindle fibers attach during division; required for proper chromatid segregation and composed of highly repetitive noncoding DNA.

Telomere

A heterochromatic structure at the ends of eukaryotic chromosomes that provides chromosomal stability and prevents the ends from degrading or sticking together.

POT Proteins

Protection of Telomere proteins that bind to the single-stranded overhang at chromosome ends to shield them from degradation and improper fusion.

Nucleosome

The simplest level of eukaryotic chromatin structure ("beads on a string"), visible under low salt conditions and composed of double-stranded DNA wrapped around eight histone molecules.

Chromatosome

A chromatin subunit consisting of a nucleosome core of eight histone proteins wrapped with DNA, locked in place by linker histone H1.

Histones

Small, positively charged proteins rich in arginine (Arg) and lysine (Lys) amino acids that bind tightly to the negatively charged DNA backbone.

Core Histones

The four types of histone proteins (H2A, H2B, H3, and H4) that form an octamer around which eukaryotic DNA winds within a nucleosome.

Histone H1

A linker histone protein that binds to linker DNA outside the nucleosome core to help lock DNA in place and stabilize the chromatosome.

Histone Tails

Positively charged groups of amino acids at the ends of histone proteins that wrap around DNA, interact with backbone phosphates, and undergo regulatory post-translational modifications.

Epigenetics

The study of stable, heritable phenotypic variation caused by changes in gene expression and chromatin structure rather than differences in the underlying nucleotide sequence.

5-Methylcytosine

A chemically modified base produced by the addition of a methyl group to position 5 of a cytosine ring, predominantly at CpG dinucleotides, that acts to repress gene expression.

CpG Dinucleotides

Cytosine-phosphate-guanine sequence pairs on DNA strands where cytosine methylation frequently occurs on both complementary strands.

Maintenance Methyltransferase

An enzyme that recognizes hemimethylated DNA following replication and adds methyl groups to the newly synthesized daughter strand to faithfully replicate the epigenetic mark.

Histone Deacetylases (HDACs)

Enzymes that remove acetyl groups from histone proteins, restoring positive charges so histones bind DNA more tightly, condensing chromatin and down-regulating gene expression.

Histone Acetylation

An epigenetic modification that masks positive charges on histone tails, weakening their interaction with DNA to produce a more open chromatin conformation that stimulates transcription.

Dnmt3 Gene

A gene in honeybees encoding a DNA methyltransferase; when repressed by royal jelly or siRNAs, reduced genomic methylation triggers development of queen characteristics.

X-Inactivation

A dosage compensation mechanism in female mammals where one X chromosome is randomly silenced early in development and clonally inherited by daughter cells via mitosis.

X-Inactivation Center (XIC)

A specific region on the mammalian X chromosome where chromosome inactivation initiates, containing regulatory noncoding RNA genes such as Xist, Tsix, Jpx, and Xite.

Xist Gene

A noncoding RNA gene in the X-inactivation center that encodes a long RNA that coats the X chromosome from which it is transcribed and recruits repressive protein complexes (such as PRC2).

Tsix Gene

A noncoding RNA gene in the XIC transcribed antisense and complementary to Xist RNA that represses Xist function to prevent inactivation of the active X chromosome.

Jpx Gene

A gene encoding a long noncoding RNA located in the X-inactivation center that stimulates the synthesis of Xist on the inactive X chromosome.

Xite Gene

A noncoding RNA gene in the X-inactivation center that promotes and sustains Tsix expression on the active X chromosome.

Polycomb Repressive Complex 2 (PRC2)

A protein complex recruited by Xist RNA that methylates histones (creating the H3K27me3 mark) to stably silence gene expression on the inactive X chromosome.

Genomic Imprinting

An epigenetic phenomenon where the expression of an allele is determined by the parent from whom it was inherited, leading to different phenotypic outcomes in reciprocal crosses.