Epigenetics and Chromatin Regulation Lecture

Vocabulary flashcards covering the key epigenetic concepts, proteins, DNA modifications, chromatin structures, sequencing methods, and imprinting disorders discussed in the lecture.

Epigenetics

The study of heritable changes in gene function that occur without alterations in the DNA sequence, often mediated by DNA methylation, histone modification, and chromatin remodeling.

DNA methylation

Addition of a methyl group to the 5-carbon of cytosine, typically at CpG sites, leading to gene repression when present in promoters.

Histone

One of a family of basic proteins (H2A, H2B, H3, H4, and linker H1) around which DNA winds to form nucleosomes.

Histone tail

The N-terminal extensions of histone proteins that protrude from the nucleosome and are subject to post-translational modifications.

Histone modification

Covalent chemical changes—such as acetylation, methylation, phosphorylation—on histone tails that influence chromatin structure and gene expression.

Histone acetylation

Attachment of acetyl groups to lysine residues on histone tails, neutralizing positive charge, opening chromatin, and promoting transcription.

Histone methylation

Addition of one to three methyl groups to lysine or arginine residues of histones; often condenses chromatin and can repress transcription (context-dependent).

Histone phosphorylation

Addition of phosphate groups to serine, threonine, or tyrosine on histones, linked to transcription, DNA repair, chromosome condensation, and cell-cycle progression.

Histone acetyltransferase (HAT/KAT)

Enzyme that catalyzes acetylation of histone lysines; generally associated with transcriptional activation.

Histone deacetylase (HDAC)

Enzyme that removes acetyl groups from histones, leading to chromatin condensation and transcriptional repression.

Methyl-CpG binding domain (MBD) proteins

Proteins that specifically bind methylated CpG sites and recruit histone-modifying enzymes and chromatin remodeling complexes to silence genes.

CpG island

Genomic region rich in CpG dinucleotides; often located near gene promoters and subject to methylation control.

Chromatin remodeling complex

ATP-dependent multiprotein machine that alters, slides, or ejects nucleosomes to regulate DNA accessibility.

Nucleosome

The basic unit of chromatin: ~147 bp of DNA wrapped 1.65 turns around an octamer of two each of H2A, H2B, H3, and H4 histones.

Chromatosome

A nucleosome plus one linker histone H1 that secures DNA entry and exit points.

Euchromatin

Relatively open, transcriptionally active chromatin; visually resembles "beads-on-a-string."

Heterochromatin

Highly condensed 30-nm chromatin fiber associated with transcriptional silencing.

TET enzymes

Ten–eleven translocation dioxygenases that oxidize 5-methylcytosine to 5-hydroxymethylcytosine and further derivatives, promoting demethylation.

5-methylcytosine (5mC)

Methylated form of cytosine generated by DNA methyltransferases; key epigenetic mark for gene silencing.

5-hydroxymethylcytosine (hm5C)

Oxidation product of 5mC formed by TET enzymes; abundant in embryonic stem cells and neurons, implicated in pluripotency and alternative splicing.

5-formylcytosine (5fC)

Further oxidation product of 5mC; can be removed by TDG-mediated base-excision repair in active demethylation.

5-carboxylcytosine (5caC)

Highest oxidation state of 5mC in the TET pathway; intermediate in active DNA demethylation.

6-methyladenine (6mA)

Methylated adenine important in prokaryotic DNA; detectable by SMRT and nanopore sequencing.

Single Molecule Real-Time (SMRT) sequencing

PacBio technology that measures DNA polymerase kinetics to identify sequence and base modifications like 6mA.

Nanopore sequencing

Technique that detects changes in ionic current as DNA passes through a nanopore, enabling direct identification of methylated vs unmethylated bases.

Chromatin immunoprecipitation (ChIP)

Method that cross-links proteins to DNA, shears chromatin, and uses antibodies to isolate protein-DNA complexes for mapping binding sites.

Imprinting

Epigenetic phenomenon where gene expression depends on parental origin, involving allele-specific DNA methylation.

UBE3A

Gene on chromosome 15 encoding ubiquitin-protein ligase E3A; maternally expressed in certain brain regions, loss causes Angelman syndrome.

Angelman syndrome

Neurogenetic disorder (maternal UBE3A loss) characterized by severe developmental delay, ataxia, speech impairment, epilepsy, and happy demeanor.

SNRPN

Small nuclear ribonucleoprotein polypeptide N gene within chromosome 15 imprinting region; paternal expression loss contributes to Prader-Willi syndrome.

Prader-Willi syndrome

Imprinting disorder from paternal deletion or maternal uniparental disomy of chromosome 15, leading to hypotonia, hyperphagia, obesity, and infertility.

ATP-dependent chromatin remodeling

Energy-intensive process by which remodeling complexes use ATP hydrolysis to reposition or exchange nucleosomes, regulating transcription.

Stem cell pluripotency

Ability of embryonic stem cells to differentiate into all cell types; maintained in part by specific epigenetic landscapes like hm5C patterns.

ENCODE project

International consortium (Encyclopedia of DNA Elements) mapping functional genomic elements, including chromatin marks, across human cell lines.