University:
Amherst College
Course:
BIOL 330 | Biochemical Principles of Life at the Molecular Level
Academic year:

2010
Views:

36

Pages:

23
Author:

trindairat0f

Chemical Biology 03 Oct 23, 2009 Gene Regulation Every Step in Gene Expression is a potential target for Regulation 20,000 genes present in all human cells subset of proteins unique to a particular cell type under a particular set of conditions Transcriptional Regulation transcription initiation Transcriptional Regulation transcription initiation Regulation is achieved by: 1) Regulatory DNA sequence • • • next to promoter up to several 1000 base-pairs “upstream” (before) promoter sometimes even in introns or “downstream” of gene • • • binds DNA double helix in a sequence-specific manner Some are Positive Regulators (“activators” and “enhancers”) Some are Negative Regulators (“repressors” and “silencers”) 2) Regulatory Protein Transcriptional Regulation Examples of DNA-binding domains of Regulatory Proteins Regulatory Proteins bind Double-stranded DNA (like TATA binding Protein) Transcriptional Regulation transcription initiation How do proteins bound so far away influence transcription machinery? Network of Regulatory Proteins ~ 2000 - 3000 genes in our genome = Transcriptional Regulatory Proteins The transcriptional activity of any given gene is determined by abundance, activity, cooperation, competition of different Regulatory Proteins The presence & activity of a regulatory protein is influenced by cell type and by extracellular environment In vertebrate cells transcriptional repression of certain genes can be reinforced by direct modification of DNA: methylation DNA methylation patterns can be faithfully inherited through rounds of DNA replication DNA methylation patterns can be faithfully inherited through rounds of DNA replication: Maintenance Methylase Enzyme locks DNA in a transcriptionally “silent” state One model for how methylation may help to silence genes Euchromatin (active) Heterochromatin (condensed, inactive) Recall that genes are scattered over many chromosomes transcribed part of gene Chr.I Chr.II Chr.III Chr.IV Recall genes are NOT polycistronic in eukaryotes (NO operons) DNA Binding Site for Regulator transcribed part of gene Chr.I Chr.II Chr.III Chr.IV Regulation of Gene Expression: Globin genes Regulation of Gene Expression: Globin genes β cluster: 1 β gene, 1 delta gene, 2 gamma genes, 1 epsilon gene (and 1 pseudogene) Regulation of Gene Expression: Globin genes Chromosome 16 Chromosome 11 α cluster: 2 α genes, 1 zeta gene, 1 theta gene (and 3 pseudogenes) β cluster: 1 β gene, 1 delta gene, 2 gamma genes, 1 epsilon gene (and 1 pseudogene) Duplication of globin genes over the course of millions of years of evolution adult Fetal hemoglobin allows evolution of placental mammals 2 different O2 transporters: Myoglobin & Hemoglobin Regulation of Gene Expression: β Globin gene cluster •Only expressed in Red Blood Cells (cell-type specific expression) •Expression changes over course of development •Locus Control Region: crammed with recognition sequences for Regulators Methylation at promoter regions also plays a role in shutting off specific genes ex, α cluster: methylated promoter

Chemical Biology 03 Central Dogma – IV

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