Section 3: Regulation of Gene Expression

Epigenetics

no change in DNA but inherited modification of genome &/or chromatin components

Majority of cancer related SNPs are in _____

Non-coding RNAs (ncRNA)

Transcription factors

proteins that bind to promoter and enhancer control regions to regulate transcription

Four Common DNA-binding domains

1. Helix-turn-helix

2. leucine zipper

3. helix-loop-helix

4. zinc finger

Methods to examine transcription factor binding

1. electrophoretic mobility shift assay EMSA;s

2. DNase foot-printing assays

3. promoter mutation reporter analysis

Steroid Hormones

pass through cell membrane and bind to intracellular receptors. In nucleus, target genes through specific response elements

Retinoic Receptor (RAR)

part of the steroid hormone receptor superfamily; a retinoid acid dependent transcription regulator, derived from vitamin A and act as transcriptional receptor

Heterochromatin

highly compacted chromatin that is not transcribed

Euchromatin

related chromatin that is open and accessible for transcription

Histone Modification

histones undergo port-translational modification

Function of Histone Acetylation

activates transcription

Function of Histone deacetyltransferases (HDAC)

repress transcription

DNA methylation

the addition of a methyl group to cytosine and is associated with gene silencing

DNA methyltransderases

• move a methyl group from S-adenosyl-methionine (SAM).

• May act to silence genes by blocking transcription factor access to DNA.

• Recruit chromatin-modifying enzymes to alter chromatin structure

• indirectly induce mutation via deamination

DNMT1

converts hemi-methylated DNA to fully methylated DNA during replication to allow methylation patterns to be inherited

DNMT3 & DNMT3b

cause methylation at new sites (de novo)

Methylbinding Domain (MBD) proteins

recruited to CpGs can interact with HDACs and chromatin remodeling enzymes