control of gene expression transcriptional post-transcriptional epigenetics and long range control
TRANSCRIPT
Control of gene expression
• Transcriptional
• Post-transcriptional
• Epigenetics and long range control
Control of gene expression
• Transcriptional–Tissue specific transcription factors –Binding of hormones, growth factors etc. to
response elements–Use of alternative promoters in a single gene
Control of gene expression
• Post-transcriptional–Alternative splicing –Alternative polyadenylation–Tissue specific RNA editing–Translational control mechanisms
Control of gene expression
• Epigenetics and chromatin structure–Allelic exclusion (rearrangements, imprinting,
X inactivation)–Long range control by chromatin structure
(position effects Pax6 in aniridia)–Cell position-dependent, short range signaling
Control of gene expression
• rRNA synthesis–Arrows indicate cleavage sites
Control of gene expression
• Initiation of transcription (RNA pol I)
Control of gene expression
• tRNA and 5s RNA promoter elements
• Initiation of transcription (RNA pol III)
Control of gene expression
• Conserved locations of promoter elements in eukaryotes
Control of gene expression
• Insulin gene promoter organization–NRE negative regulatory element–CRE cAMP response element
Control of gene expression
• HS-40 alpha-globin regulatory site–Tissue specific regulation (many sites)
Control of gene expression
• Structural domains in transcription factors–HTH–HLH–Zn Finger–Alpha-helix
Control of gene expression
• Binding of conserved motifs to double helix
Control of gene expression
• Steroid receptors and response elements–GR–ER–PR–RAR–TR–VDR
Control of gene expression
• Transcription regulation by glucocorticoids
Control of gene expression
• Target gene expression via signal transduction–Protein kinase: hormonal signaling through
cAMP-pt kinase A pathway–Cytoplasmic transcription factor NF kappa B
and translocation to the nucleus
Control of gene expression
• Major Classes of Cell Surface Receptor–G protein coupled–Serine-Threonine kinase–Tyrosine kinase–Tyrosine kinase associated JAK (janus protein
kinase) activity in JAK-STAT signaling–Ion channel-linked
Control of gene expression
• Secondary Messengers in Cell Signaling–Cyclic AMP (cAMP)–Cyclic GMP (cGMP)–Phospholipids/Ca
Control of gene expression
• The IRE binding protein and iron-response elements (IREs)
Control of gene expression
• Genes with multiple promoters–Dystrophin has eight promoters
Control of gene expression
• Differential RNA splicing–Wt1 Wilm’s tumor (four splice forms)–Calcitonin gene (tissue specific products)
Control of gene expression
• Tissue specific RNA editing–Apolipoprotein B gene (rare)
Control of gene expression
• Methylation and gene expression–Largely confined to CpG dinucleotides–CpG islands–Methylation patterns change during
development–Sex-specific regulation
Control of gene expression
• Methylation–CpG islands
Control of gene expression
• Methylation–Changes in methylation throughout
development
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Control of gene expression
• Methylation–Sex-specific regulation of the Dnmt1 methyl
transferase gene–1so somatic–1sp spermatocytes–1oo oocytes
Control of gene expression
• Transcriptional repression by histone deacetylation–Mediated by methylation–Methylated CpG’s bound by MeCP2 repressor
Control of gene expression
• Gene clusters–Coordinated switching –Locus control region–Globin genes
Control of gene expression
• Imprinting–DNA methylation key component–Selective expression of genes–Nonequivalence of maternal and paternal
genomes
Control of gene expression
• Monoallelic expression from biallelic genes –Allelic exclusion according to parent of origin
• Genomic imprinting
–Allelic exclusion independent of parent of origin
• X-chromosome inactivation• Programmed DNA rearrangement• Unknown mechanism
Control of gene expression
• Programmed rearrangement –Ig and TCR loci in B and T lymphocytes
Control of gene expression
• Programmed rearrangement –Ig heavy chain locus on 14q32
• 86 variable (V) sequences• 30 diversity (D) sequences• 9 joining (J) segments• 11 constant (C) sequences
Control of gene expression
• Programmed rearrangement –Light chain synthesis
• Somatic recombination V to J• RNA splicing VJ to C
–Heavy chain synthesis• Two sequential somatic recombination events yield
DJ and VDJ• RNA splicing VDJ to C• Somatic recombination VDJ to different C
(switching)
Control of gene expression
• Inversion or deletion based splicing–Ig kappa light chain
• V-J splicing
