Epigenetics: Mechanisms, X-Inactivation, and Imprinting

Comprehensive vocabulary flashcards covering concepts of epigenetic gene regulation, cis- and trans-mechanisms, X-inactivation, histone variants, DNA methylation, and genomic imprinting.

Epigenetics

The study of mechanisms that lead to a change in gene expression that can be passed from cell to cell but do not involve a change in the sequence of DNA.

Epimutation

A heritable change in gene expression that does not involve an alteration in the underlying sequence of DNA.

DNA Methylation

An epigenetic modification where methyl groups are attached to cytosine bases in DNA, typically inhibiting transcription when occurring near promoters.

Chromatin Remodeling

The movement or eviction of nucleosomes that alters transcription levels near promoters or facilitates large-scale changes in chromatin structure.

Covalent Histone Modification

The addition of chemical groups (such as acetylation or phosphorylation) to specific amino acid side chains on the amino-terminal tails of histones to enhance or inhibit transcription.

Feedback Loop (Epigenetics)

An epigenetic mechanism where the activation of a gene encoding a transcription factor results in that transcription factor continually stimulating its own expression.

Cis-Epigenetic Mechanism

An epigenetic mechanism in which an epimutation is maintained during cell division only at the original site, leaving the second copy of the gene unaffected (e.g., genomic imprinting and X-inactivation).

Trans-Epigenetic Mechanism

An epigenetic mechanism in which an epimutation is transmitted to both copies of a gene via a diffusible molecule, such as a transcription factor or non-coding RNA.

Dosage Compensation

A mechanism that equalizes the expression of X-linked genes between males and females.

X-Inactivation

The dosage compensation mechanism in female mammals where one of the two X chromosomes is randomly inactivated and condensed into a Barr body during embryogenesis.

Barr Body

The densely compacted, inactivated X chromosome found in somatic cells of female mammals.

X Inactivation Center (XIC)

The locus on the mammalian X chromosome from which X-inactivation initiates and spreads in both directions towards the telomeres; contains the Xist and Tsix genes.

Xist Gene

The only gene that remains active on the inactivated X chromosome, encoding a $17\text{ kb}$ long non-coding RNA (lncRNA) that lacks open reading frames and coats the chromosome.

Tsix Gene

A gene actively transcribed on the active X chromosome in the opposite direction of Xist, hypothesized to recruit DNA methyltransferase to silence the Xist promoter.

Pluripotency Factors

Transcription factors that stimulate the transcription of Tsix and inhibit the transcription of Xist prior to X-inactivation.

Repeat C (Xist RNA)

A repetitive sequence within Xist RNA that binds to a tethering protein bound to the Xic to tether Xist RNA to the inactive X chromosome.

hnRNP-U

A DNA-binding protein that binds numerous AT-rich sequences within the inactive X chromosome DNA and complexes with Xist RNA during the spreading phase.

Repeat A (Xist RNA)

A repetitive sequence within Xist RNA that recruits chromatin-silencing proteins to promote gene repression and compaction into a Barr body.

PRC2

A complex recruited to the inactive X chromosome by Repeat A of Xist RNA that catalyzes the histone modification $\text{H3K27me3}$.

MacroH2A

A core histone variant abundant on the inactivated X chromosome in female mammals that functions in chromatin compaction.

$$\text{H1}^0$$

A linker histone variant associated with chromatin compaction and gene repression.

H2A.Z

A core histone variant found in nucleosomes that flank the transcriptional start site of promoters, playing a functional role in gene transcription.

H2A.Bbd

A core histone variant that promotes open chromatin and plays a role in gene activation.

cenH3

A core histone variant localized to centromeres that is involved in the binding of kinetochore proteins.

H3.3

A core histone variant that promotes open chromatin structure and gene activation.

X Hyperactivation

The dosage compensation mechanism in male Drosophila involving the upregulation of gene expression from the single X chromosome.

X Hypoactivation

The dosage compensation mechanism in female/hermaphrodite Caenorhabditis elegans involving the partial repression of gene expression from both X chromosomes.

Epigenetic Inheritance

A heritable epigenetic change in gene expression and chromatin structure that is passed from parent to offspring without changing the DNA nucleotide sequence.

Maintenance Methyltransferase

An enzyme that selectively methylates hemimethylated DNA during replication using the methylation pattern of the parent strand as a template.

De Novo DNA Methyltransferases

Enzymes, such as DNMT3A and DNMT3B, that establish completely new DNA methylation patterns on unmethylated DNA.

Genomic Imprinting

An epigenetic process in which allele expression is determined by parent of origin, driven by sex-specific DNA methylation patterns established during gametogenesis.

Imprint Control Region (ICR)

A differentially methylated region located near an imprinted gene that regulates its parent-of-origin-specific expression.

Differentially Methylated Region (DMR)

A genomic region that exhibits different levels or patterns of DNA methylation depending on parental origin, such as in the Igf2 locus.

CTCF (CCCTC-Binding Factor)

A regulatory protein that binds to CCCTC DNA sequences in ICR and DMR regions to mediate chromatin loop domain formation.

Imprintome

The collection of imprint regulatory elements in the human genome that control the expression of imprinted genes.

Prader-Willi Syndrome (PWS)

A human disorder caused by a deletion in chromosome $15$ leading to the loss of paternal expression of the SNRPN and NDN genes, characterized by reduced motor function, obesity, and small hands/feet.

Angelman Syndrome (AS)

A neurodevelopmental disorder caused by a deletion in chromosome $15$ leading to the loss of maternal expression of the UBE3A gene, characterized by hyperactivity, unusual seizures, repetitive muscle movements, and mental deficiencies.