Eukaryotic Gene Regulation

5 mechanisms Chromatin Structure Transcriptional Posttranscriptional Translational Posttranslational

Chromatin Structure Which of these is more accessible to the kitten? A

Unacetylated histones Acetylated histones Figure 15.7 Nucleosome Histone tails Unacetylated histones Acetylated histones Figure 15.7 A simple model of the effect of histone acetylation 4

Heterochromatin is like a ball of yarn! RNA polymerase cannot reach heterochromatin! Euchromatin = the sweet stuff! (DNA accessible to RNA polymerase

Barr Bodies An X chromosome is packed away as heterochromatin Why only in females? Evidence of Chromatin structure regulating gene product

Transcriptional Control Just like prokaryote, # 1 way to control gene activity Much more complex!

Major Players Promoter – low level of gene activity Transcription factors – proteins that regulate Transcription activators – bind to enhancers

The rest of the Major Players Enhancers – DNA can be far from promoter! Responsible increased level of gene activity Repressors – much less of a role in eukaryotes https://www.dnalc.org/resources/3d/13-transcription-advanced.html silencers

Enhancer (distal control elements) Figure 15.8a Enhancer (distal control elements) DNA Upstream Proximal control elements Poly-A signal sequence Transcription start site Exon Intron Exon Intron Exon Promoter Figure 15.8a A eukaryotic gene and its transcript (part 1) Transcription termination region Downstream 11

Poly-A signal sequence Transcription start site Figure 15.8b-2 Proximal control elements Poly-A signal sequence Transcription start site Exon Intron Exon Intron Exon DNA Promoter Transcription Poly-A signal Primary RNA transcript (pre-mRNA) Exon Intron Exon Intron Exon 5 Cleaved 3 end of primary transcript Figure 15.8b-2 A eukaryotic gene and its transcript (part 2, step 2) 12

Poly-A signal sequence Transcription start site Figure 15.8b-3 Proximal control elements Poly-A signal sequence Transcription start site Exon Intron Exon Intron Exon DNA Promoter Transcription Poly-A signal Primary RNA transcript (pre-mRNA) Exon Intron Exon Intron Exon 5 Cleaved 3 end of primary transcript RNA processing Figure 15.8b-3 A eukaryotic gene and its transcript (part 2, step 3) Intron RNA Coding segment mRNA G P P P AAAAAA 3 Start codon Stop codon 5 Cap 5 UTR 3 UTR Poly-A tail 13

Distal control element Enhancer TATA box Figure 15.10-2 Promoter Activators Gene DNA Distal control element Enhancer TATA box General transcription factors DNA- bending protein Group of mediator proteins Figure 15.10-2 A model for the action of enhancers and transcription activators (step 2) 14

Distal control element Enhancer TATA box Figure 15.10-3 Promoter Activators Gene DNA Distal control element Enhancer TATA box General transcription factors DNA- bending protein Group of mediator proteins RNA polymerase II Figure 15.10-3 A model for the action of enhancers and transcription activators (step 3) RNA polymerase II Transcription initiation complex RNA synthesis 15

After Transcription RNA processing Splicing

Translational Control Longevity of RNA

Translational Control RNA induced silencing complex microRNAs bind to mRNA Degrade or inhibit translation

Post translation Protein is present and active! Cell can degrade it at different rate (proteosomes) Cyclin proteins