1. H3.3 and its role in Pediatric Gliomas By: Connor Belson Biology 445

2. Histone 3 Protein H3 is one of the proteins that make up the Nucleosome, which plays a significant role in control of gene expression H3.3 is a known variant of H3

3. Chromatin Organization

4. Histone Role in Gene Expression

5. Histone Tail Modifications

6. Histone 3.3 Role in Gene Expression

7. H3.3 Promotes Cell Cycle Progression

8. Pediatric Glioma What is it? Abnormal growth of cells within the Central Nervous System Symptoms? Diagnosis? 1.History/Physical Exam 2.CT Scan/MRI 3.Biopsy

9. K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas

10. Inhibition of PRC2 activity by a gain-of-function H3.3 mutation (K27M) found in pediatric glioblastoma.

11. Mutations in gene encoding H3.3, at or close to G34, show an increased expressed of MYCN

12. Increased MYCN does what?

13. Genetics of Pediatric Glioma

14. Treatments Prognosis and treatment can be based on anatomical location of tumor or on severity of malignancy and proliferation

15. Summary H3 proteins are one of several histones that make up the nucleosome H3 and other histones are post translationally modified Cells with mutations in H3.3 can cause improper regulation of gene expression Histone H3.3 mutations upregulate MYCN

16. References http://www.ncbi.nlm.nih.gov/pubmed/19322538 http://www.uspharmacist.com/content/s/125/c/20820/ http://www.aboutcancer.com/brain_low_grade.htm http://cancerdiscovery.aacrjournals.org/content/3/5/512/F2.expansion.html http://cancerdiscovery.aacrjournals.org/content/3/5/512.full-important!! http://cancerdiscovery.aacrjournals.org/content/3/5/512.full-important http://www.biologia.uniba.it/eca/NEWSLETTER/NS-11/02-Article.html http://genesdev.cshlp.org/content/15/18/2343.full http://www.nature.com/nri/journal/v2/n3/fig_tab/nri747_F1.html http://www.nature.com/ng/journal/v45/n12/fig_tab/ng.2814_F1.html http://www.ncbi.nlm.nih.gov/pubmed/23603901 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656328/ http://www.ncbi.nlm.nih.gov/pubmed/23603901 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656328/ http://www.cancernetwork.com/brain-tumors/two-distinct-subtypes-pediatric-glioma-identified http://www.nature.com/nrc/journal/v13/n6/full/nrc3527.html http://openi.nlm.nih.gov/detailedresult.php?img=3076323_pone.0018064.g004&req=4 http://edoc.hu-berlin.de/dissertationen/irlbacher-horst-2005-07-14/HTML/chapter1.html http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193428/