H3.3 and its role in Pediatric Gliomas

By: Connor BelsonBiology 445

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

Chromatin Organization

Histone Role in Gene Expression

Histone Tail Modifications

Histone 3.3 Role in Gene Expression

H3.3 Promotes Cell Cycle Progression

Pediatric GliomaWhat is it?Abnormal growth of cells within the Central Nervous System

Symptoms?

Diagnosis?1. History/Physical Exam2. CT Scan/MRI3. Biopsy

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

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

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

Increased MYCN does what?

Genetics of Pediatric Glioma

Treatments

• Prognosis and treatment can be based on anatomical location of tumor or on severity of malignancy and proliferation

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

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://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.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/