Hierarchy of Chromatin Structure Flashcards
Hierarchy of Structure
Nucleosome, 30 nm fiber, Chromatin Loop, Miniband, Chromosome
Number of Nuclei Erythrocyte
0 via Extrusion
Number of Nuclei Cardiocyte, Hepatocyte
1-2 via Nuclear Division
Number of Nuclei Osteoclast
3-10 via Fusion of Precursors
Number of Nuclei Skeletal Myocytes
100+ via Fusion of Myoblasts
Chromatin Types and Function
Heterochromatin: Highly dense, transcriptionally inactive, 10%
Euchromatin: Less dense, can be active
Nucleosome structure
200 bp of DNA, octamer of proteins from core families (H2A, H2B, H3 and H4) with DNA wraapped around this bead (140 BP). High in K+ and R+ residues. Linked with H1 (60 BP)
Histone Acetylation
Neutralizes positive charge on K and R, repulsing histones from DNA sites
Histone Methylation
H3 causes formation of heterochromatin
Histone Phosphorylation
Condensation of chromatin for mitosis
Location of histone modifications
Amino-Terminal Tails
DNA Methylation
Methyl addition to cytosine on 5’ carbon of base in CpG dinucleotides, blocking TFs from binding, conducted by DNA methyltransferases (DNMTs)
DNA Methylation/Chromatin Condensation Cascade
Methyl CpG binding proteins (MBPs) find methylated CpGs
MBPs recruit histone deacetylases (HDACs) and Histone Methyltransferases (HMTs)
HDACs increase K and R charge, causing histones to more tightly bind to DNA, reducing expression
HMTs methylate histones to completely silence expression
Effect of histone modification on tumor suppressor genes
Epigenetic modifications been shown to suppress tumor suppressor genes, causing high cell growth
Treated with DNMT and HDAC inhibitors
DNMT Inhibitors
5-azacytidine (Vidaza) and 5-aza 2’ deoxycytidine (Decitabine)
HDAC inhibitors
SAHA (Vorinostate), Phenylbityrate, Valproic acid
Histone Acetyl Transferase Cascades
HATs are recruited by TFs to acetylate histones for expression, also one or two histones may be dissolved for opening the promoter sequence
30-Nanometer Fiber structure
6 Nucleosomes form 1200 bp fiber (per solenoid turn) , H1 facilitates construction, 30 nm refers to solenoid diameter
Loop structure
On average 50 30 nm fibers coiled into loop for 60,000 bp, leading to supercoiling
Bases of loops are attached to nuclear matrix which have machinery for gene regulation/expression
Loop function
Downstream and upstream interaction of gene allows for it to interface with nuclear matrix, regulating expression
Minibands structure
18 loops to form roughly 10^6 bp
Tandems of loops that encircle chromosome axis
Mitotic Chromosomes structure
On average 75 minibands come together so 75 mil BP
Includes centromere and two telomeres
Centromere structure
Repetitive DNA in middle of chromosomes
Telomere structure
Repetitive DNA (GGGTTA in humans) which cap ends of chromosome
Telomere function
Shortens with each division until cell senescence is achieved in somatic cells
Germ line cells have telomerase to continue permitting division
When telomerase is activated in somatic cells it results in cell immortality
