Control of Gene Expression

just key vocab.

operon

DNA region containing a promoter, an operator, and the genes controlled by them

operator

DNA segment (usually positioned w/in promoter/ between promoter and rest of genes) regulating functionally related genes as a single, shared on/off switch

repressor protein

binds the operator and blocks transcription by preventing RNA polymerase from proceeding, made by a spearate regulatory gene. Other molecules can change whether it is active

Repressible operons/corepressor

_______ _______s are usually on. A _______ activates the repressor, which then binds the operator and switches transcription off

Trp operon/tryptophan

corepressor example, which encodes enzymes for tryptophan synthesis.

• When _____ is abundant, it binds the trp repressor and acts as a corepressor. This is logical for an anabolic pathway: the end product reduces production of the enzymes used to make it.

inducible operons/inducer/lac

_______ _______s are usually off. An _______ inactivates the repressor and allows transcription. Example: the ___ operon, whose genes encode proteins involved in lactose metabolism.

• Lactose (more precisely, its derivative allolactose) acts as an inducer by inactivating the lac repressor.

activator/CRP/CAP

• Lac operon and glucose

  • The lac operon is subject to both negative control by the lac repressor and positive control by the _____ (also called __).

Proximal/distal/enhancer/mediator

______ control elements are near the promoter.

_____ control elements can be far from the promoter or within introns; groups of distal elements are called _______.

• DNA bending can bring distant activators close to the promoter. _____ proteins help connect activators with the transcription machinery.

Differential gene expression

expression of different genes by cells with the same genome, resulting in differences between cell types

Euchromatin/Heterochromatin

Chromatin structure relatively open and accessible to transcription machinery// condensed and usually transcriptionally inactive

DNA methylation//methyl

• Addition of _____ groups to certain bases in DNA, generally associated with reduced transcription. Removal of extra can turn on some genes. 

• can contribute to long-term gene silencing, genomic imprinting (it regulates expression of mat/paternal alleles of certain genes at the start of development), and X-chromosome inactivation.

• //______// patterns can be copied to daughter DNA after replication.

• Abnormal patterns occur in some cancers

Histone/acetylation/methylation/phosphorylation

______ modification 3 types:

________ neutralizes positive charges on lysine residues (on + Lys in histone tails), loosening chromatin and generally promoting transcription.

________ can either promote or reduce transcription, depending on the location and context.

________ (next to a methylated amino acid) can also alter chromatin structure and gene expression, loosening chromatin

Epigenetic

________ inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence. ________ changes can be reversible and are influenced by cellular and environmental factors.

Specific transcription factors/control elements/activators/repressors

S_________ t_______ f_______ regulate particular genes by binding to noncoding DNA sequences called _______ _________.
Transcription factors may act as:

• ________, which promote transcription.

• ___________, which inhibit transcription, for example by blocking activator binding or altering chromatin.

General transcription factors (TFs)

assemble at the promoter and help recruit and position the polymerase

ubquitin/proteasome

Cells mark selected proteins for degradation by attaching _________. The proteins are then recognized and broken down by the ________ into peptides, which can be further degraded or recycled.

miRNAs (MicroRNAs)

___RNAs are produced from primary RNA transcripts containing hairpin structures:

1. Drosha cuts hairpins from the primary transcript. - 

2. Dicer trims them into short double-stranded RNA fragments of about 22 nucleotides. - 

3. Argonaute helps remove one strand(; the remaining strand joins proteins to form a silencing complex, such as miRISC). - 

• Small, single-stranded RNA molecules that bind to complementary/target mRNA and degrade mRNA or block its translation. 

  • __RNAs are thought to regulate roughly 50% of human genes.

siRNAs (Small interfering RNAs)/interference/i

__RNAs originate from long, linear dsRNA (double stranded RNA) precursors; similar to miRNAs in size and function
The RNA-guided silencing complex binds complementary mRNA:

• A close or complete match can lead to mRNA degradation.

• A partial match can inhibit translation, often by blocking ribosome access.

• RNA ________ (RNA_) is gene silencing caused by it; this is also used experimentally to disable genes and study their function.

piRNAs (Piwi-interacting RNAs)

associate with PIWI proteins and commonly originate from repetitive DNA or transposons ("jumping genes" or transposable element is a segment of DNA that can change its position within a genome). 

• They help suppress transposon expression and can help reestablish DNA methylation patterns during gamete formation.

lncRNAs (Long noncoding RNAs)/XIST

• typically at least 200 nucleotides long and can be much longer. They may help assemble regulatory complexes or alter chromatin.

  • During X-chromosome inactivation, the __RNA ___ coats an X chromosome and promotes its condensation into a largely inactive Barr body.

Cell determination/Cell differentiation

irreversible commitment of a cell to a particular fate// process by which the cell acquires the structures and functions associated with that fate. Tissue-specific mRNAs are among the first signs of differentiation.

Morphogens/Morphogenesis

are unevenly distributed signals that help direct tissue shape and development, a type of Cytoplasmic determinants, which are made by Maternal-effect genes

Cytoplasmic determinants

 are unevenly distributed maternal substances (RNAs, proteins, etc) in the unfertilized egg. As the egg divides, daughter cells receive different combinations, influencing their developmental fates; produced by maternal-effect gene expression

Induction

signal molecules from embryonic cells cause transcriptional changes in nearby target cells,
occurs when signaling molecules from one group of embryonic cells affect nearby cells, changing their gene expression and fate

Pattern formation/Positional information

the development of spatial organization of tissues and organs of an organism, begins with the establishment of the major axes (anterior-posterior, dorsal-ventral, right-left) // molecular cues that control pattern formation, informs a cell its location relative to the body axes and to neighboring cells

1/ has been extensively studied in Drosophila melanogaster

Homeotic genes/Homeosis

help determine which body parts form at particular locations and control aspects of pattern formation/refers to one body part developing in the position of another

bicoid/morphogen/morphogen gradient

Example of Maternal-effect genes:

The ________ gene is a maternal-effect gene that helps establish the anterior (front) end of the fly.

• ____ mRNA is localized near the anterior end of the egg. After fertilization, it is translated, and ____ protein forms an anterior-to-posterior gradient.

  • The gradient acts as a ___________, helping specify anterior structures. (└______: establish embryo’s an embryo’s axes and other features of its form; _________ hypothesis) 

Maternal-effect genes

 encode products placed in the egg by the mother; the mother’s genotype can determine the early offspring phenotype.

mRNA localization

an efficient way to concentrate a protein in a specific region: localized mRNA can be translated repeatedly at that site

embryonic lethals

death causing mutation during embryogenesis

Proto-oncogenes/oncogene

are normal genes whose products promote cell growth and division/ is a cancer-causing form of a gene that promotes excessive cell growth or division.

Ras/proto-oncogene

•  ___is a ____-_______ that encodes a G protein relaying growth signals from cell-surface receptors through a protein-kinase cascade.

  • Normally, ___ is activated by binding GTP and then inactivates itself by hydrolyzing GTP to GDP.

  • Mutations that prevent inactivation can leave ___ persistently active, driving cell division without a growth signal.

p53/tumor-suppressor gene

___ is a _________ ______ that responds to DNA damage.
Nonfunctional __ allows cells with damaged DNA to continue dividing. It can activate DNA repair, inhibit cell-cycle progression, or trigger cell death if damage is irreparable.