Epigenetics, Chromatin Dynamics, and Gene Regulation

Vocabulary practice flashcards covering dynamic chromatin, nucleosome structure, DNA methylation, genomic imprinting, X-chromosome inactivation, histone modifications, and transcriptional activation from Chapter 12.

Epigenetics (Modern Definition)

The study of heritable changes in gene function and chromosome behavior that cannot be explained by alterations in the underlying DNA sequence.

Agouti Mouse Epigenetic Model

A biological model where genetically identical mice display distinct coat colors ranging from yellow to brown based on maternal dietary folate levels during critical developmental periods, which permanently alters coat pigmentation through DNA methylation.

Epigenetic Landscape (Conrad Hal Waddington)

A conceptual model proposed to resolve how epigenesis could be influenced by genetics, aimed historically at reconciling disagreements between embryologists and geneticists.

David Nanney's Definition of Epigenetic

A concept proposed to explain mating type determination in isogenic Tetrahymena, defining epigenetics as a non-nuclear heritability of long-term cellular memory carried in the cytoplasm rather than the nucleus.

Robin Holliday's Definition of Epigenetics

Originally proposed with John Pugh as a mutational mechanism involving changes in DNA methylation rather than base sequence, which was later broadened to refer to transcriptional regulation.

Arthur Riggs's Definition of Epigenetics

A definition that restricted the term to molecular processes heritable through cell division, explicitly including both mitotic and meiotic transmission to establish the multigenerational definition of epigenetics.

Nucleosome

The fundamental repeating subunit of chromatin, consisting of approximately $150\,\text{bp}$ of DNA wrapped $1.7\,\text{times}$ around an octameric histone protein core.

Histone Core Octamer

A protein complex composed of two copies each of the four core histones: H2A, H2B, H3, and H4, around which genomic DNA winds.

Histone H1

A linker histone that binds to the entry/exit sites of DNA on the nucleosome, facilitating the compaction of nucleosome arrays into higher-order chromatin structures.

DNA Methylation

A covalent post-replication modification wherein methyl groups are enzymatically added to DNA bases without altering the primary nucleotide sequence, typically repressing transcriptional activity.

5-Methylcytosine ($5\text{meC}$)

The most prevalent form of covalent DNA methylation in mammalian cells, formed by the addition of a methyl group to carbon 5 of a cytosine ring.

CpG Dinucleotides

DNA regions where a cytosine nucleotide is immediately followed by a guanine nucleotide joined by a phosphodiester bond; the primary sequence site for DNA methylation in mammals.

CpG Island

A short stretch of genomic DNA exhibiting a higher frequency of CG dinucleotides than surrounding regions, commonly located in gene promoter regions and typically unmethylated in transcriptionally active states.

DNMT1

A maintenance DNA methyltransferase responsible for copying established methylation patterns onto newly synthesized daughter strands during DNA replication.

DNMT3A and DNMT3B

De novo DNA methyltransferases responsible for establishing new DNA methylation marks on previously unmethylated CpG sites during development.

DNMT3L

A regulatory protein related to DNMT enzymes that lacks catalytic activity but is critical for maternal genomic imprinting by stimulating and directing DNMT3A and DNMT3B.

Hemimethylated DNA

A double-stranded DNA duplex in which only one of the two complementary strands carries methyl groups at target CpG sites, typically generated immediately following semiconservative replication.

Methyl-CpG-Binding Proteins (MBDs)

Epigenetic reader proteins that selectively recognize and bind 5-methylcytosine residues, recruiting transcriptional repressors and chromatin-modifying enzymes to mediate gene silencing.

Genomic Imprinting

An epigenetic mechanism that results in monoallelic gene expression in a parent-of-origin-specific manner, where the allele from one parent is transcriptionally silenced via heavy methylation and chromatin condensation.

Epigenetic Reprogramming

The extensive, genome-wide erasure of parental DNA methylation marks in primordial germ cells (PGCs) followed by sex-specific de novo methylation during gamete development and early embryogenesis.

Prader-Willi Syndrome (PWS)

A genetic condition caused by the inheritance of a paternal deletion of approximately $4\,\text{Mb}$ on chromosome 15 (15q11-q13), characterized by hypotonia, short stature, small hands and feet, obesity, hypogonadism, and mild to moderate mental retardation.

Angelman Syndrome (AS)

A neurodevelopmental disorder resulting from the maternal inheritance of a $4\,\text{Mb}$ deletion on chromosome 15 (15q11-q13), characterized by severe mental retardation, seizures, and an ataxic gait.

Dosage Compensation

The regulatory process that equalizes the expression dosage of X-linked genes between XX mammalian females and XY males.

Lyon Hypothesis

The principle formulated by Mary Lyon in the 1960s stating that one of the two X chromosomes in each somatic cell of female mammals is randomly and permanently inactivated during early embryonic development.

Barr Body

A condensed, transcriptionally inactive X chromosome visible as a densely staining heterochromatic mass against the nuclear membrane in mammalian female somatic cells.

Tortoiseshell / Calico Pattern Mosaicism

A visible phenotype in female cats heterozygous for X-linked black and tan coat-color alleles, produced by random, fixed X-chromosome inactivation in individual embryonic cell lineages.

X Inactivation Center (XIC)

A designated locus at band q13.2 on the human X chromosome that controls the initiation and propagation of X-chromosome inactivation.

XIST (X-Inactive-Specific Transcript)

A gene mapped within the XIC that produces a $17\,\text{kb}$ non-coding RNA that coats the chromosome in cis from which it was transcribed, triggering heterochromatinization and transcriptional silencing.

Histone Acetyltransferases (HATs)

Enzymatic 'writers' that catalyze the addition of acetyl groups to lysine residues on histone amino-terminal tails, neutralizing their positive charge to promote chromatin decondensation and transcriptional activation.

Histone Deacetylases (HDACs)

Enzymatic 'erasers' that remove acetyl groups from lysine residues on histone tails, restoring their positive charges and promoting chromatin condensation and gene silencing.

Epigenetic Writers, Erasers, and Readers

The tripartite enzymatic machinery of the epigenetic code: writers add marks (e.g., acetylases, methylases), erasers remove marks (e.g., deacetylases, phosphatases), and readers recognize marks (e.g., bromodomain, chromodomain, MBD proteins).

Histone Code Hypothesis

The concept that post-translational covalent modifications to histone proteins, predominantly on their flexible N-terminal tails, act combinatorially to regulate chromatin condensation and direct gene transcription.

Chromatin Remodeling

The dynamic alteration of chromatin architecture to modulate access of condensed genomic DNA to regulatory transcription machinery proteins, mediated by histone PTMs and ATP-dependent remodeling complexes.

SWI-SNF Complex

An ATP-dependent multi-protein chromatin-remodeling complex that utilizes energy from ATP hydrolysis to slide, eject, or restructure nucleosomes away from promoters.

Enhanceosome

A higher-order nucleoprotein complex formed by the cooperative binding of multiple sequence-specific regulatory transcription factors to an enhancer, functioning synergistically to activate transcription.

GCN5

A histone acetyltransferase co-activator recruited by the enhanceosome that acetylates flanking nucleosomes (nuc 1 and nuc 2) to facilitate chromatin opening.

Co-activator CBP

A transcriptional co-activator recruited to the enhanceosome following nucleosome acetylation that participates in recruiting RNA polymerase II and the SWI-SNF complex to nudge nucleosome 2 by $37\,\text{bp}$, exposing the TATA box.