control of gene expression transcriptional post-transcriptional epigenetics and long range control

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