Eukaryotic Gene Expression and Control

Flashcards covering the mechanisms of gene expression control in eukaryotes and bacteria, including chromatin remodeling, transcription initiation, RNA interference, and the genetic basis of cancer.

Differential gene expression

The process responsible for forming specialized cell types by having cells with the same genome express different sets of genes.

Chromatin

A structure in eukaryotes where DNA is wrapped around proteins, primarily histones.

Chromatin remodeling

The process of transitioning DNA from a condensed or "closed" state to a decondensed or "open" state before transcription can begin.

Histones

The most abundant DNA-associated proteins that complex with DNA to form chromatin.

Nucleosome

A structural unit of chromatin consisting of about $200$ base pairs of DNA wrapped almost twice around a core of eight histone proteins.

H1

A specific histone protein that "seals" DNA to each set of histone proteins within a nucleosome.

30-nanometer fiber

A tightly packed structure formed by interactions between H1 histones and other nucleosomes, named for its width of $30\,\text{nm}$.

DNases

Enzymes that cut DNA, used to test chromatin accessibility because they cannot effectively cut DNA when it is tightly wrapped in condensed chromatin.

DNA methyltransferases

A group of enzymes that add methyl groups ($-CH_3$) to cytosine residues in DNA.

DNA methylation

A mechanism that triggers chromatin condensation; methylated CpG sequences are recognized by proteins that lead to a "closed" chromatin state.

CpG

A specific DNA sequence in mammals involving a C next to a G in one strand, which is often the target for DNA methylation.

Histone code hypothesis

The proposition that particular combinations of histone modifications on specific amino acids set the state of chromatin condensation for a particular gene.

Histone acetyltransferases (HATs)

Enzymes that add acetyl groups to positively charged lysine residues in histones, usually promoting decondensed chromatin.

Histone deacetylases (HDACs)

Enzymes that remove acetyl groups from histones, causing chromatin to condense and effectively acting as an "off" switch for transcription.

Chromatin-remodeling complexes

Macromolecular machines that harness the energy in ATP to reshape chromatin by sliding nucleosomes or knocking histones off DNA.

Epigenetic inheritance

The collective term for any mechanism of inheritance that is due to something other than differences in DNA sequences, such as patterns of DNA methylation.

Hnf4a

A gene associated with diabetes that codes for a regulator of genes involved in glucose uptake, which can be silenced by maternal nutrition through epigenetic markers.

Core promoter

The specific sequence in eukaryotes where RNA polymerase binds, often exemplified by the TATA box.

TATA box

The most intensively studied core promoter sequence in eukaryotes, consisting of a short stretch of DNA.

TATA-binding protein (TBP)

The protein that binds to the TATA box in the core promoter as the first step in initiating transcription.

Regulatory sequences

DNA sections that allow the binding of proteins to control the initiation of transcription, including promoter-proximal elements and enhancers.

Promoter-proximal elements

Regulatory sequences located close to the core promoter that are associated with specific genes to allow for differential expression.

Enhancers

Regulatory DNA sequences that can be located at vast distances (over $100,000$ base pairs away) from the promoter and provide positive control of transcription.

Silencers

Regulatory DNA sequences that inhibit transcription when bound by specific repressor proteins, providing an element of negative control.

Transcriptional activators

Regulatory transcription factors that bind to enhancers and promoter-proximal elements to trigger transcription.

Repressors

Regulatory transcription factors that bind to silencers to shut down transcription.

Regulatory transcription factors

Collective term for proteins (activators and repressors) that bind to enhancers, silencers, and promoter-proximal elements to regulate gene expression.

General transcription factors

Proteins that interact with the core promoter and are necessary for transcription but do not provide much in the way of gene-specific regulation.

Mediator

A large complex of proteins that acts as a bridge between regulatory transcription factors, general transcription factors, and RNA polymerase II.

Alternative splicing

A post-transcriptional mechanism where different combinations of exons are included in the mature mRNA, allowing one gene to code for multiple proteins.

Isoform

Any of the different proteins or mature mRNAs that result from alternative splicing of the same primary transcript.

RNA interference (RNAi)

A mechanism where a small single-stranded RNA held by a protein complex binds to a complementary mRNA to destroy it or block its translation.

MicroRNA (miRNA)

A small single-stranded RNA derived from cellular genes that participates in RNA interference by targeting complementary mRNAs.

Dicer

The RNA-processing complex in the cytoplasm that trims the loop from precursor miRNAs to create double-stranded miRNA fragments.

RNA-induced silencing complex (RISC)

A protein complex that unwinds double-stranded miRNA, retains the guide RNA, and uses it to target and either cut or block mRNA translation.

Short interfering RNAs (siRNAs)

Small RNAs generated from long double-stranded RNAs (often viral or transposable elements) that function via RISC to silence invasive genes.

PIWI-interacting RNAs (piRNAs)

Small single-stranded RNAs that primarily block the movement of transposable elements and can regulate chromatin condensation.

Ubiquitin

A small polypeptide added to proteins to mark them for destruction.

Proteasome

A macromolecular machine that recognizes proteins with a ubiquitin tag and cuts them into short segments.

Tumor suppressors

Proteins that stop or slow the cell cycle when conditions are unfavorable; the loss of their function via mutation can lead to cancer.

Proto-oncogenes

Normal genes that stimulate cell division but can be converted into oncogenes if regulation becomes defective.

Oncogene

A mutant allele of a proto-oncogene that promotes cancer by causing cells to divide continuously.

p53

A tumor suppressor and transcription factor known as the "guardian of the genome" that induces cell cycle arrest, DNA repair, or apoptosis.

Apoptosis

Programmed cell death, which can be triggered by p53 if DNA damage is too severe to repair.

Operon

In bacteria, a set of genes of related function controlled by a single promoter and transcribed into a single polycistronic mRNA.

Operator

The specific region of DNA in a bacterial operon where regulatory proteins bind to control transcription.

Inducer

A small molecule that inactivates a repressor protein to turn "on" transcription in an inducible operon.

Co-repressor

A small molecule that binds to a repressor protein to activate it, turning "off" transcription in a repressible operon.