Overview Function can turn transcription on/off can ↑ or ↓ rate of transcription can act in cis or trans cis = regulation near gene locus DNA binding sequence a mutated cis regulatory element can result in gene that is constitutively on or off trans = regulation from gene locus transcription factor protein because it acts at a distance a good allelic copy can compensate for a mutated copy Mechanisms of control modify RNAp binding stability transcription factors function modify basal transcription levels two types general must bind to DNA and RNAp to begin baseline transcription of most every gene e.g. TFIID binds TATA box and RNAp II specific acts through enhancers and silencers can regulate specific gene responses structure DNA binding domain can be zinc fingers, helix-turn-helix, helix-loop-helix, or leucine zippers regulatory element binding domain e.g. binds hormone, ion, other transcription factors, etc. modify RNAp accessibility to DNA histone modifiers histone acetylases (HATs) open DNA and ↑ transcription histone deacetylase (HDACs) close DNA and ↓ transcription see Chromatin Structure topic imprinting methylation effectively shuts a gene off often irreversible some genes methylate a gene locus on paternal or maternal chromosome allows only one allele to be active e.g. Prader-Willi/Angelman syndrome see Epigenetics topic inactivation of a chromosome condensation of # of X chromosomes - 1 to form Barr bodies e.g. Turner's Syndrome (XO) the patient would have no Barr bodies as they only have 1 X chromosome increase number of gene copies more sites for RNAp to bind common in oncogenes Embryonic gene regulation sonic hedgehog (SHH) gene mutations causes holoprosencephaly (HPE) failure of midline brain to separate into right and left homeobox (HOX) genes control proper timing of gene activation paired box (PAX) genes mutations cause Klein-Waardenburg syndrome presentation neural crest abnormalities deafness variation in pigmentation forelock of white hair patches of different colored skin dystopia canthorum broad nasal root Examples of gene regulation peroxisome proliferator-activated receptors (PPARs) controls fat metabolism turned on by endogenous ligands fatty acids, prostaglandins also turned on by exogenous ligands fibrates, thiazolidinediones bind PPRE region in DNA clinical importance fibrates given to hyperlipidemic patients to ↑ transcription of lipoprotein lipase also used in treatment for Zellweger syndrome