Gene Regulation

Contributes to heterochromatin formation. Creates binding sites for specific proteins that promote chromatin compaction. Silences genes.

Cytosine methylation in CpG sequences

less compact CNA, efficiently transcribed

Euchromatin

the DNA of an individual A difference in DNA sequence between individuals is referred to as a difference in genotype

Genotype

more compact DNA, limited transcription

Heterochromatin

Contributes to euchromatin formation by weakening interaction with DNA (loss of positive charge). Acts over a region of a gene or a chromosome

Lysine acetylation in N-termini of histones

Depending upon particular residue modified, may stimulate formation of either euchromatin or heterochromatin. Does not alter charge on side chain. Modifications recruit specific proteins that change chromatin state.

Methylation of lysine and arginine residues in histones

the consequences of an individual's DNA Differences in appearance, behavior, biochemistry, etc., between individuals are referred to as differences in phenotype.

Phenotype

Steps in Gene Expression That May Be Regulated

Rate of transcription Rate of RNA processing Rate of RNA nuclear export (eukaryotes) Rate of RNA degradation Rate of translation of proteins Rate of protein degradation

In terms of disease, genetic variation among individuals explains:

Why only some individuals develop a particular disease. Why individuals differ in their innate ability to conquer a disease. Why the effectiveness of a particular drug varies among individuals. Why the side-effects of a particular drug varies among individuals.

Transcriptional Control Regulation by cAMP

cAMP response element-binding protein (CREB) binds promoters of genes activated by cAMP, e.g., genes for glucose synthesis in liver. CREB binds DNA only when Ser133 is phosphorylated. CREB binding stimulates transcription. When glucose is absent, [cAMP] increases. cAMP activates protein kinase A, which phosphorylates CREB at Ser133.

Usually a nucleic acid sequence or structure. Physically linked (part of the same molecule) to the target that is regulated.

cis-acting element

binds near promoter; increases affinity of RNA polymerase for promoter (cooperative interaction). binds DNA only when complexed with cAMP. cAMP synthesized when glucose absent; cAMP concentration drops when glucose is present.

cyclic AMP-binding protein (CAP)

___is a protein that binds free iron (too much free iron is toxic).

ferritin

binds to specific DNA sequence called the operator. binding physically prevents RNA polymerase binding to promoter. binds operator in absence of lactose. binds lactose and dissociates from DNA

lac repressor

trans-acting factor(s) binds target and decreases gene expression, e.g., decreased transcription rate, decreased frequency of translation, increased degradation rate.

negative control

Mutations can cause

no detectable change in phenotype. a minor change in protein or RNA function or in gene expression. a drastic change in protein or RNA function or in gene expression.

trans-acting factor(s) binds target and increases gene expression, e.g., increased transcription rate, increased frequency of translation, decreased degradation rate.

positive control

Usually a protein that binds a cis-acting sequence. Free to move in the cell; binding activity may be modified by small molecule, chemical modification (e.g., phosphorylation), etc.

trans-acting factor

Regulated attachment of _____ targets proteins to _____ for degradation

ubiquitin proteasome