Chapter 12 - Gene Regulation

Forming compact structures maintains euchromatic

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Unformatted text preview: atic regions, and increases access to DNA template Events that Occur at a Promoter Following the Binding of a transcriptional activator 4 o o o o o Transcription factors (such as GR) bind , recruiting coactivators which facilitate the assembly of the transcription preinitiation complex Acetyl groups are added to specific lysine resudes by enzymes called histone acetyltransferases (HATs) Acetylated histones recruit chromatin remodelling complex Chromatin remodelling complexes use energy from ATP hydrolysis to alter nucleosome structure (more open and accessible state) and location TFIID can now bind which initiates transcription Chromatin Remodelling o Chromatin remodelling can occur in different ways: sliding, conformational change, histone exchange or histone dissociation Regulating Transcription o o o RNA polymerases are also bound to transcriptionally silent genes that initiate transcription but do not transition to elongation These polymerases are ready for transcription but are posed by inhibitory factors Gene transcription at the level of elongation may be important in activation of genes Transcriptional Repression Transcriptional Repression o o o o o o o o Histone deacetylases (HDACs) remoce acetyl groups and repress transcription HDACs are subunits of larger complexes corepressors They are recruited to specific gene loci by transcription factors that cause the targeted gene to be silenced The histone tails in the promoter region of active chromatin are acetylated when a transcritptional repressor binds to its DNA binding site it recruits a corepressor complex and an associated HDAC activity HDAC removes acetyl groups from the histone tails a separate protein adds methyl groups to the K9 residue on H3 histone tail the loss of acetyl and addition of methyl groups leads to chromatin inactivation, and therefore gene silencing Transcriptional repression is not well understood but a key factor is DNA methylation which is carried out by DNA methyltransferases which silences transcription Changes in DNA methylation pattern often is associated with diseases Methylation patterns of gene regulatory regions change during cell differentiation Once the pattern of methylation is established, it is maintained thorough cell division by an enzyme that methylates the daughter DNA strands according to the pattern of the parental strands Genomic Imprinting o o o o o o Is unique to mammals Activity of certain genes, called imprinted genes, depends on whether they originated with the sperm or the egg Active and inactive versions of imprinted genes differ in their methylation patterns Methylation state is not affected by normal developmental methylation changes so genes that are on will stay on even in adult tissues Major exception is germ cells where inherited imprints are erased and then re-established Disturbances in imprinting patterns have been implicated in a number of rare human genetic disorders 5 Processing Level Control o o Protein diversity can be generated by alternative splicing Alternative splicing can become complex, allowing different combinations of exons in the final mRNA product Alternative Splicing o o o o o o o o o Whether an exon is included in the final mRNA depends on selection of 3 and 5 splice sites by splicing machinery Many factors influence this machinery strength of splice sites Some sites are weak and can be bypas...
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This document was uploaded on 04/10/2014.

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