Cell and molec Chapter 8 (gene expression)

Cell differentiation

The process of a STEM cell becoming other cell types. Liver, neuron, etc. Caused by gene expression

Gene Expression

Favoring transcripting certain genes over others. Mainly caused by producing different proteins. Changes in size, shape, behavior, and function

Inducing Transcription

Turning transcription “on” via promoters on the DNA

Housekeeping proteins

Proteins commonly produced in all cells of an organism. Structural proteins of chromosomes, RNA polymerases, DNA repair enzymes, ribosomal proteins, enzymes involved in glycolysis and other basic metabolic processes, and many of the proteins that form the cytoskeleton

Specialized Proteins

Responsible for the cell’s distinctive properties

How many genes does a typical human differentiated cell express?

5,000-15,000 out of 25,000 total

Main control of gene expression in Eukaryotes

Transcriptional Control

Transcriptional Control

Controlled by proteins binding to regulatory DNA sequences

Regulatory DNA Sequences

DNA Sequences that switch the gene “on” or “off.” EX: The Promoter. Present in prok. and euk. Prok bond CLOSE to promoter, Euk FAR AWAY from promoter

Where do transcriptional regulators bind?

Major Groove of the DNA

Transcriptional Regulators

Proteins that bind to the Major Groove of the DNA helix to control transcription. Amino acids contribute to how strong the interaction is. Different proteins recognize different nucleotide sequences

Bonds that Transcriptional Regulators form

Hydrogen bonds, ionic bonds, and hydrophobic interactions with
the edges of the bases. Some of the tightest and most specific bonds in the body

Motif

Common folding patterns in transcriptional regulators (proteins). How the regulators usually bind to DNA

Homeodomain

Motif common in euk. Three consecutive alpha helices

Zinc Finger Motif

Motif often found in clusters. An alpha helix and beta sheet joined together by a molecule of Zinc

Leucine Zipper Motif

Two alpha helices that form a Dimer. It grips the DNA like a clamp

Dimer

Consists of two structurally similar molecules, making a single molecular entity

Dimerization

doubles the number of protein−DNA contacts, increasing
the regulatory control of transcription

Main transcriptional control in Prokaryotes

The Operator, situated in the Promoter, switching an Operon on and off. This allows for the expression of the Operon to be coordinated

Repressor Protein

in Prok. Responds to the concentration of a protein and binds to the Operator region to block transcription if there is excess

Main “signal” to toggle transcription in Prokaryotes

The concentration of a protein

Activator Protein (prok)

in Prok. NEEDED for the Promotor to work. Helps RNA polymerase initiate transcription, binds to DNA

Catabolite activator protein (CAP)

Binds to cyclic amp (cAMP) to switch CAP genes on. Responds to low Glucose concentration

Lac Operon

Inducible system in Prok that breaks down complex sugars into simple sugars. Signaled to turn on by high lactose (complex sugar), repressed when lactose is absent

Lac Repressor

Binds to Lac Operon when there is no lactose in the bacteria cell

LacZ

first gene of the Lac operon, encodes the enzyme β-galactosidase, which breaks down lactose to galactose and glucose

Activator Protein (euk)

Binds to the Enhancer in DNA. The DNA loops itself so the Activator can touch the Mediator & RNA transcription complex

Enhancer

Binding site in DNA for eukaryotic activator proteins

Mediator

A complex that acts as a go-between of the Activator protein and transcriptional complex in Eukaryotes after the DNA makes a loop

Topological associated domains (TADs)

The loops that DNA are arranged in for eukaryotes. The “knot” is held together by proteins

Histone acetylases

in Euk. Attracted by transcriptional activators. Attaches an acetyl to the histone, opening it, promoting gene expression

Histone deacetylases

in Euk. Attracted by repressors. Removed the acetyl added to a histone, closing it, reducing gene expression

Histone methylases

Add a methyl to the histone, attracting heterochromatin (tigher packing), making the gene hard to access, reducing gene expression

Two major ways Euk Transcriptional Regulators do their job

1) Directly affecting how RNA poly and general transcription factors assemble around the promoter. 2) Locally modify the chromatin in promoter regions

Cell Memory

Changes in gene expression being maintained and carried over into daughter cells

Positive feedback loop

a transcription regulator activates transcription of its
own gene in addition to that of other cell-type-specific genes

Regulatory proteins

Proteins that induce their own creation as part of cell memory. The decision to make new Regulatory Proteins is made after each division

Combinatorial Control

the way that groups of regulatory proteins work together to determine the expression of a single gene

Pluripotent Stem Cells

cells that are capable of giving rise to specialized cell types

iPS Induced Pluripotent Cells

cells that look and behave like pluripotent
stem cells but are artificially induced in a lab.

Faithful propagation of a condensed
chromatin structure

Second way of cell memory. The daughter DNA has half the histone modifications, a protein recognizes the pattern and adds the other half back to the daughter DNA

DNA Methylation / epigenetic inheritance

Third way of cell memory. 5-methylcytosine is made by methylizing a Cytosine next to a Guanine. The other “side” the DNA that is unmethylated in the daughter DNA will be recognized and given a methyl. SILENCES this region b/c more heterochromatin

Maintenance methyltransferase

Responsible for maintaining CG methylization in daughter cells

Riboswitches

in Prok. Short sequences in a number of mRNAs change their conformation when bound to small molecules to regulate their own transcription and translation

miRNA (micro RNA)

Endogenous “noncoding” RNA. Binds to RISC protein and becomes single stranded 3’-5’. Targets complementary mRNA for destruction. Don’t have introns, get 5’ cap and poly-A tail

RISC Protein

RNA-induced silencing complex (RISC). Binds to miRNA

siRNA (small interfering RNA)

Targets foreign RNA after it was cleaved by Dicer. It binds to RISC and then destroys the foreign RNA. Packeged into RITS

RNA interference (RNAi)

Process of eliminating potential RNA invaders with miRNA and siRNA

Transcriptional Silencing

Triggered by RNAi, shutting off the synthesis of foreign RNA and proteins

RITS (RNA-induced
transcriptional silencing)

The protein complex that contains siRNA. Binds to single stranded siRNA and attaches to RNA being made by active foreign RNA polymerase. It modifies nearby histones to promote heterochromatin, silencing the region

Xist

A known type of lncRNA, long noncoding RNA. A key player in X-inactivation, silencing the X chromosome

CRISPR

Clustered Regularly Interspaced Short Palindromic Repeat. Bacteria use snRNA to record past infections and CRISPR records it in the CRISPR locus

snRNA (small noncoding RNA)

Used in Bacteria to help protect themselves from past viruses

crRNAs (CRISPR RNAs)

“Guide” RNAs made from the CRISPR locus to combat a virus. Binds with CRISPR-associated (Cas) enzymes to cleave viral DNA