Eukaryotic Gene Regulation, Transcription, and Chromatin Development

Vocabulary practice flashcards covering eukaryotic transcription initiation, general transcription factors, mRNA processing, chromatin remodeling, histone modifications, and developmental gene regulation.

RNA Polymerase I

A eukaryotic RNA polymerase that transcribes ribosomal RNA (rRNA) genes, carrying out functions analogous to RNA polymerase in prokaryotes.

RNA Polymerase II

A 12-subunit eukaryotic enzyme that transcribes protein-coding genes into mRNA as well as certain snRNA genes.

RNA Polymerase III

A eukaryotic enzyme responsible for transcribing tRNA, the $5\text{S}$ rRNA subunit, and snRNAs involved in RNA splicing.

TATA Box

A core promoter consensus sequence ($\text{TATAAA}$) located around $-30$ relative to the transcription start site, bound directly by the TATA-binding protein (TBP).

CAAT Box

A eukaryotic promoter element located at approximately $-80$ ($\text{GGCCAATCT}$), recognized and bound by the CAAT box transcription factor (CTF).

GC Element

A promoter consensus element located without a fixed location between $-200$ and $+1$, bound by the transcription factor SP1.

Downstream Promoter Element (DPE)

A core promoter regulatory sequence located from $+28$ to $+33$ that is specifically recognized and bound by TAF6 and TAF9.

General Transcription Factors (GTFs)

A group of essential proteins (including TFIID, TFIIA, TFIIB, TFIIF, TFIIE, and TFIIH) strictly required to form the RNA Polymerase II pre-initiation complex at eukaryotic promoters.

Non-General Transcription Factors

Regulatory proteins that are not strictly essential for pre-initiation complex formation but assist RNA Polymerase II in locating the TATA box.

TFIID

A multi-protein general transcription factor consisting of TBP and TAF subunits that binds specifically to the TATA box.

TFIIA

A general transcription factor that stabilizes TBP binding to DNA and prevents repressor proteins from binding.

TFIIB

A general transcription factor that helps position RNA Polymerase II precisely at the $+1$ transcription start site.

TFIIF

A general transcription factor that binds and escorts RNA Polymerase II directly to the gene promoter.

TFIIE

A general transcription factor that recruits TFIIH to the pre-initiation complex and modulates its activity.

TFIIH

A multi-subunit general transcription factor possessing helicase activity to unwind DNA and kinase activity to phosphorylate the CTD of RNA Polymerase II, initiating transcription.

Poised State

The transcriptional state where the RNA Polymerase II pre-initiation complex has assembled at the promoter but remains unphosphorylated, with no transcription yet underway.

Paused State (RNA Pol II)

The transcriptionally stalled state resulting from CDK-7 phosphorylating Serine 5 on the RNA Pol II C-terminal domain (CTD), which also recruits mRNA processing machinery.

CDK-9

The cyclin-dependent kinase that phosphorylates Serine 2 on the RNA Polymerase II CTD, releasing the enzyme from the paused state into productive elongation.

Enhancers

Regulatory DNA sequences located upstream (~ $-500$), downstream, or within introns that bind activators and loop across distances to contact promoters, increasing transcription efficiency.

Silencers

Regulatory DNA sequences located upstream or downstream from promoters that bind tissue-specific repressors and fold/loop to contact promoters and suppress transcription.

Insulators

Regulatory DNA elements that bind proteins like CTCF to organize loops, preventing inappropriate cross-talk by insulating genes from nearby activating or silencing signals.

Pierre Robin Syndrome

A congenital disorder presenting with a cleft palate, reduced lower jaw, and posteriorly displaced tongue, caused by a mutation in the $Sox9$ enhancer that prevents binding of the transcription factor Twist1.

5' m7G Cap

A modified guanine cap added to the $5'$ end of pre-mRNA by guanylyl transferase (GTase) and subsequent methyltransferases after 20–30 nucleotides are synthesized; essential for translation, ribosome orientation, and protecting transcript stability.

Polyadenylation

The enzymatic cleavage of pre-mRNA downstream of an $\text{AAUAAA}$ consensus signal followed by the addition of 200–300 adenine residues by PolyA polymerase (PAP) and PABII, ensuring transcript stability and cytoplasmic transport.

5' Splice Site (Donor Site)

The boundary at the $5'$ end of an intron defined by the consensus sequence $\text{GURAGU}$, containing a nearly invariant $\text{GU}$ dinucleotide.

3' Splice Site (Acceptor Site)

The sequence at the $3'$ end of an intron containing a pyrimidine-rich tract followed by an invariant $\text{AG}$ dinucleotide.

Branch Site

An intron sequence located 20 to 40 nucleotides upstream of the $3'$ splice site characterized by a pyrimidine-rich region and an invariant branch point adenine ($\text{A}$).

Lariat Structure

A looped splicing intermediate generated via transesterification when the $2'\text{-OH}$ of the branch point adenine attacks the guanine at the $5'$ donor splice site.

Alternative Splicing

A post-transcriptional mechanism where exons are differentially selected or excluded, allowing a single gene to encode multiple distinct mature mRNA and protein isoforms.

Nucleosome

The structural subunit of chromatin comprising approximately 147 bp of DNA wound around a histone octamer composed of two copies each of H2A, H2B, H3, and H4.

Euchromatin

Loosely compacted, 'open' chromatin that remains accessible to transcription factors and RNA polymerases to support active gene transcription.

Heterochromatin

Densely compacted, 'closed' chromatin that restricts transcriptional machinery access and inhibits gene expression.

Constitutive Heterochromatin

Chromatin regions that remain permanently condensed, closed, and transcriptionally silent in all cell types, commonly characterized by H3K9 di- or tri-methylation.

Facultative Heterochromatin

Regions of chromatin that dynamically transition between condensed (heterochromatin) and decondensed (euchromatin) conformations depending on developmental stage or lineage, often marked by H3K27 di- or tri-methylation.

Chromatin Modifiers (Writers, Erasers, Readers)

Enzymatic machinery where 'Writers' add chemical groups to histone tails, 'Erasers' remove them, and 'Readers' recognize and bind specifically modified histones.

Chromatin Remodelers

ATP-dependent multi-protein complexes that alter nucleosome positioning via sliding, exposing enhancer or promoter motifs to allow transcription factor binding.

Histone Acetylation

The addition of acetyl groups to lysine residues (such as K9 and K27) on histone tails, neutralizing their positive charge, loosening DNA interaction, and promoting active transcription.

H3K4 Tri-methylation

A post-translational histone methylation mark that acts as an indicator of active gene promoters within open euchromatin.

Position Effect Variegation (PEV)

The variable silencing of a gene resulting from its abnormal relocation adjacent to heterochromatin via chromosomal rearrangements such as inversions.

Suppressors of Variegation [Su(Var)]

Genes that normally promote heterochromatin formation; when mutated, heterochromatin spreading is impaired, allowing neighboring genes (like $w^+$) to be expressed and yielding redder fly eyes.

Enhancers of Variegation [E(Var)]

Genes that normally reduce heterochromatin to facilitate gene activation; when mutated, heterochromatin spreads more extensively, silencing target genes and resulting in whiter fly eyes.

ChIP-Seq

An experimental technique combining formaldehyde crosslinking of chromatin, sonication, antibody-based immunoprecipitation of modified histones/transcription factors, crosslink reversal, and next-generation sequencing.

DNA Methyltransferases (DNMTs)

Enzymes that covalently transfer methyl groups directly to DNA to establish transcriptional repression and gene silencing, often by recruiting histone deacetylases (HDACs).

MeCP2

A methyl-CpG-binding protein that binds methylated DNA sequences to repress transcription; human mutations in this gene cause the severe neurological disorder Rett syndrome.

Totipotent

Early embryonic stem cells that retain the full developmental capability to differentiate into every cell type of the entire organism, including embryonic tissues and the placenta.

Pluripotent

Embryonic stem cells (such as blastula-stage cells) capable of generating all embryonic cell lineages but unable to give rise to extra-embryonic placental tissues.

Multipotent

Stem cells restricted to generating a limited range of specialized cell types within a dedicated tissue or lineage, such as hematopoietic stem cells.

Induced Pluripotent Stem Cells (iPSCs)

Differentiated adult somatic cells reprogrammed back into an embryonic-like pluripotent state via the exogenous expression of four transcription factors: Oct4, Sox2, c-Myc, and Klf4.

Theory of Differential Gene Activity

The fundamental concept that all somatic cells preserve genomic constancy, and morphological diversity arises because each cell type expresses a distinct subset of genes.

ZRS Enhancer

A limb-specific modular enhancer located inside the $Lmbr1$ gene that directs Sonic Hedgehog ($Shh$) expression in developing limb buds; deletions ($\Delta A, \Delta B, \Delta C$) lead to limb reduction in pythons.

Eyeless (ey) / Pax6

A master transcription factor gene in Drosophila ($ey$) and vertebrates ($Pax6$) controlling eye development, whose targeted ectopic misexpression can induce functional eyes on other body parts.

Homeotic (Hox) Genes

Conserved transcription factors arranged in clusters whose order on the chromosome matches their anterior-to-posterior expression pattern, providing segment identity along the body axis.

Polycomb Group (PcG) Proteins

Epigenetic repressor complexes that establish facultative heterochromatin to maintain the stably silenced 'OFF' state of non-selected lineage genes in differentiated cells.

Trithorax Group (TrxG) Proteins

Chromatin-modifying enzymes (including H3K4 methyltransferases) that counteract Polycomb-mediated repression to actively maintain target developmental genes in the 'ON' state.

Somatic Cell Nuclear Transfer

A cloning procedure demonstrating genomic equivalence by transferring a differentiated somatic cell nucleus into an enucleated egg cell, as shown by John Gurdon in frogs and Ian Wilmut with Dolly the sheep.