CPET had yet to receive any Spruce Creek applications for their programs. I’m told there are several applications that went in recently. CPET wants us to know that they have funding for about 30 scholarships and that the lack of funding should not be a reason to fail to apply. SSTP is only for rising Seniors but there is a new 2 week program in biomedical science for rising Juniors.

Can genes be turned on and off in cells? Each cell expresses, or turns on, only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation. Gene regulation is an important part of normal development. Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments. Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood. Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time. http://ghr.nlm.nih.gov/handbook/howgeneswork/geneonoff Genetics Home Reference

Chapter 18 Eukaryotic Gene Regulation NUCLEUS Chromatin Chromatin modification Complex It’s not just about turning a gene on or off The amount of protein product is regulated Production of the protein must be coordinated with multiple inputs Regulation varies greatly in different cell types and is responsible for maintaining specific cell types Regulation can occur at any location on the pathway DNA Gene available for transcription Gene Transcription RNA Exon Primary transcript Intron RNA processing Tail Cap mRNA in nucleus Transport to cytoplasm CYTOPLASM mRNA in cytoplasm Degradation of mRNA Translation Polypeptide Protein processing Active protein Degradation of protein Transport to cellular destination Activity: Control of Gene Expression Cellular function

State of Chromatin Can Impact Gene Expression Histones undergo chemical modifications that change chromatin organization https://www.youtube.com/watch?v=eYrQ0EhVCYA euchromatin - loosely packed chromatin – most of the time except mitosis & meiosis The transcription machinery can readily access and express these genes heterochromatin - a few regions of chromatin (centromeres and telomeres) always condensed Difficult for the cell to express genetic information in these regions Regulation at this level: …tends to be long-term. A skin cell may permanently shut down expression of genes only needed in neurons …tends to involve a large region of DNA, often encompassing more than one gene Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though highly conserved, it is nevertheless the most variable histone in sequence across species.

Chromatin Can be Modulated by Histone Modifications Adding methyl groups - methylation – condenses chromatin – blocks gene expression Acetylation of histone tails promotes loose chromatin structure that permits transcription Chromatin Can be Modulated by Histone Modifications Histone tails Amino acids available for chemical modification DNA double helix (a) Histone tails protrude outward from a nucleosome

Gene Expression Can be Controlled by Transcription Initiation If transcription never begins, the protein is never made. Conversely, if RNA pol is strongly attracted to the promoter, more transcript will be produced. This sort of regulation can be accomplished in many ways

Gene Expression Can be Controlled by Transcription Initiation Chromatin-modifying enzymes may close or open DNA near the promoter to transcription machinery. Transcription Factors - RNA pol helpers that bind near the promoter (proximal control elements.) Usually, this assist RNA pol in binding the promoter, therefore they are activators. Enhancers – Proteins that bind far from the promoter and influence it’s activity (distal control elements). These may increase or decrease transcription. Activity: Control of Transcription

Gene Expression Can be Controlled by Transcription Initiation Promoter Activators Gene DNA Distal control element Enhancer TATA box RNA polymerase binding site The TATA box (Goldberg-Hogness box) is a DNA sequence in the promoter region a that is bound by transcription factors. RNA polyermase recognizes this collection of transcription factors and binds. Why have a TATA box? Why doesn’t RNA polymerase bind directly to a promoter sequence without helpers? Or does it? Figure 18.9 A model for the action of enhancers and transcription activators Fig. 18-9-1

Gene Expression Can be Controlled by Transcription Initiation Promoter Activators Gene DNA Distal control element Enhancer TATA box General transcription factors DNA-bending protein Figure 18.9 A model for the action of enhancers and transcription activators Group of mediator proteins Fig. 18-9-2

Gene Expression Can be Controlled by Transcription Initiation

Combinatorial Control of Gene Activation Enhancer Promoter Albumin gene Control elements specific combinations of control elements activate transcription Crystallin gene LIVER CELL NUCLEUS LENS CELL NUCLEUS Available activators Available activators Figure 18.10 Cell type–specific transcription Albumin gene not expressed Albumin gene expressed Crystallin gene not expressed Crystallin gene expressed (a) Liver cell (b) Lens cell Fig. 18-10

Coordinately Controlled Genes Gene Expression Can be Controlled by Transcription Initiation Coordinately Controlled Genes Each eukaryotic gene has is own promoter and control elements Genes for the same process may be scattered all over the genome, but may have the same control element combination This way when the transcription factors that turn on one of these genes are produced, all the genes in the process are transcribed.

Animation: mRNA Degradation Gene Expression Can be Controlled by Transcription Initiation mRNA Degradation After transcription initiation and transcription of the primary transcript, gene expression can be controlled by Leaving the mRNA stable Quick degradation of mRNA mRNA lifespan = amount protein made determined by sequences in the leader and trailer (untranslated)regions Animation: mRNA Degradation

Translation Initiation Gene Expression Can be Controlled by Transcription Initiation Translation Initiation regulatory proteins can block initiation of translation https://www.youtube.com/watch?v=3S3ZOmleAj0 Bozeman gene regulation

Animation: Blocking Translation Protein Processing and Degradation After translation, protein cleavage and modification are controlled. Some proteins are stored in an inactive form because they are needed quickly. Proteins involved in wound healing, for example. Proteasomes - giant protein complexes that degrade protein molecules. This will immediately stop the action of the protein. Animation: Blocking Translation

Proteosome degrades a protein. Proteasome and ubiquitin to be recycled Ubiquitin Proteasome Protein to be degraded Ubiquitinated protein Protein fragments (peptides) Protein entering a proteasome Figure 18.12 Degradation of a protein by a proteasome Fig. 18-12

Noncoding RNAs These are RNA transcripts that regulate gene expression MicroRNAs (miRNA) Small, single-stranded, bind to mRNA and degrade it or block translation Small Interfering RNAs (siRNA) RNAi = RNA interference – RNA inhibits gene expression Can impact heterochromatin formation and block large chromosomal regions

What Is a Gene? Revisiting the Question A discrete unit of inheritance A region of specific nucleotide sequence in a chromosome A DNA sequence that codes for a specific polypeptide chain or RNA Review: Control of Gene Expression Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Ethylene, fruit ripening and gene expression Read: Fruit Ripening, pg. 84 https://www.qiagen.com/geneglobe/pathwayview.aspx?pathwayID=169; http://www.scielo.br/img/revistas/bjpp/v17n3/a02fig01.jpg