Topic 7: The Organization and Control of Eukaryotic Genomes

Chromatin complex of DNA and proteins Nucleosome ”beads on a string”; basic unit of DNA packing Consists of DNA wrapped around 8 histone proteins and held together by another •histone protein (positively charged amino acids phosphates of DNA are negatively charged) Help to supercoil chromosomes and regulate transcription. Animation of organization of DNA with histones (detailed) http://biostudio.com/demo_freeman_dna_coiling.htm http://www.dnalc.org/view/15483-DNA-packaging-3D-animation-with-basic-narration.html Heterochromatin •highly condensed interphase DNA (can not be transcribed) Euchromatin •less compacted interphase DNA (can be transcribed)

Skill: Utilization of molecular visualization software to analyse the association between protein and DNA within a nucleosome. See page 348 of IB text and follow instructions: http://www.rcsb.org/pdb/home/home.do

Non-coding and Repetitive DNA Some regions of DNA do not code for proteins (used to be called “junk DNA” This DNA has other important functions… Gene expression regulation Introns Telomeres : protect DNA and prevent degradation at ends. Code for tRNA molecules Repetitive sequences Ex. GTTAC…. Ex. tandem repeats used in DNA profiling (these are repeated a different # of times in different individuals) About 97%*of human DNA *Campbell and Reece estimate Why telomeres are necessary Some is repetitive DNA Nucleotide sequences that are repeated many times in a genome May help organize chromatin into chromosomes (ex. High concentration of repetitive DNA in centromere regions)

Theory of Knowledge Discussion Highly repetitive sequences were once classified as “junk DNA” showing a degree of confidence that it had no role. To what extent do the labels and categories used in the pursuit of knowledge affect the knowledge we obtain?

Control of Gene Expression Nucleosomes help regulate transcription Gene expression is regulated by proteins that bind to specific base sequences in DNA. (see examples below) http://www.pbs.org/wgbh/nova/body/epigenetics.html Epigenetics Video Why Necessary? Cell Differentiation (ex. Stem cells become specialized) Cells only express a fraction of their genes at one time. (3-5% on avg. in humans)

Control of Gene Expression Methylation affects gene expression by preventing transcription Turns genes off

Control of Gene Expression The environment of a cell and of an organism has an impact on gene expression http://www.pbs.org/wgbh/nova/body/epigenetics.html Epigenetics Video

Nature of science: Looking for patterns, trends and discrepancies— There is mounting evidence that the environment can trigger heritable changes in epigenetic factors.

End of IB Stuff

Methods of control Chromatin modification Regulation of Transcription DNA packaging (heterochromatin vs. euchromatin DNA methylation--attachment of methyl groups (-CH3) to DNA bases turns off DNA (prevents transcription) Histone acetylation– attaching acetyl groups to histones– turns on DNA by loosening histone attachment Regulation of Transcription Transcription factors bind to DNA and stimulate transcription Post-transcriptional regulation (alternative mRNA splicing, control of translation and protein processing to make a functional protein)

Molecular Biology of Cancer Mutations in genes that control cell cycle. Oncogene--•cancer-causing genes Proto-oncogene •normal cellular genes involved in cell growth and division. May convert to oncogene How? 1-movement of gene; chromosome fragments that have rejoined incorrectly 2-amplification; increases the number of copies of proto-oncogenes 3-proto-oncogene point mutation; protein product more active or more resistant to degradation Tumor-suppressor genes •changes in genes that prevent uncontrolled cell growth (cancer growth stimulated by the absence of suppression) ex. p53 gene