Biochemistry

1. Histone Proteins and Genome
Imprinting

2. Introduction
Histone proteins: Histones are a special
group of proteins found in the nuclei of
eukaryotic cells responsible for DNA
folding and chromatin formation.

3. Chemically they are-
 highly alkaline basic proteins
 Histones are positively charged
 abundance of positive amino-acids, arginine
and lysine

4. Classes of Histones:
• There are two main classes of Histones:
• Core Histones
• Linker Histones
Core Histones:
In core histones following families are included
• H2A
• H2B
• H3
• H4
• Two of each of these core histone proteins assembles to
form one octameric nucleosome core particle, and 147 base
pairs of DNA wrap around this core particle.
contain more lysine
contain more arginine

5. Linker Histones:
Linker histone included:
 H1
 H5
 The linker histone protein H1 binds the nucleosome at
the starting and ending sites of the DNA, thus locking
the DNA into place and help in the formation of higher
order structure.
 H5 histiones are individual proteins involve in the
packaging of specific region of DNA.
highest lysine/arginine ratio

6. Function of the histone protein in
a chromosome
 The DNA is housed in chromosomes in the form
of nucleosomes
 It is basic unit of chromosome or chromatin fiber.
It is DNA duplex coiled around a core of eight
histone proteins
 Positively charged histones are linked with
negative charged phosphate groups of DNA

7.  Some histone proteins function as spools for the thread-like
DNA to wrap around
 looks like beads on a string

8.  The nucleosomes + H1 histones = 30 nm spiral
Solenoid
• it maintains the chromosomal
structure

9. Modifications…
 Acetylation
Acetyl functional group
 Methylation
Methyle group
 Phosphorylation
 It has been proposed that these modifications
result in a ‘code’ which can be read by proteins
involved in gene expression and other DNA
translations

10. Histone Acetylation & Deacetylation
• Histone acetylation
• – Histone acetyl transferases (HATs)
• Adds acetyl groups to histone tails
• Reduces positive charge and weakens interaction of histones
with DNA
• Facilitates transcription by making DNA more accessible to
RNA polymerase II
• Histone deacetylation
• – Histone deacetylases (HDACs)
• Removes acetyl groups from histone tails
• Increases interaction of
DNA and histones
• Represses transcription

11. Acetylation
• It is the introduction of an Acetyl functional group to the
Lysine amino acid of the histone tail.
• These reactions are catalyzed by enzymes with "histone
acetyltransferase" (HAT) or "histone deacetylase"
(HDAC) activity.

12. Effects of Acetylation
 -ve charge on histone
 reduces affinity of tail for adjacent nucleosomes
 creating a transcription permissive environment
 increase the access of transcription factors

13. Methylation
 It is the introduction of an Methyl functional group to
Lysine or Arginine of the histone tail.
 These reactions are catalyzed by enzymes with "histone
methyltransferase”
 ‘Arg’ can be methylated once or twice, and ‘Lys’ once,
twice of thrice.

14. Histone Methylation
• Histone methylation
• Histone methyl transferases (HMTs)
– Histone lysine methyl transferases(HKMTs)
Methylate lys (K) residues
• Protein argenin methyl transferase (PRMTs)
Methylate arge(R) residues
• Methylation can result in activation or repression of expression
 trimethylation of histone H3 at lysine 4 (H3K4) is an active mark
for transcription
 dimethylation of histone H3 at lysine 9 (H3K9), a signal for
transcriptional silencing

15. Effects of methylation
• Methylation does not neutralize charge but recruit silencing
or regulatory proteins that bind methylated histones.
• Chromodomain containing proteins interact with methylated
histone tails.
• transcription repression

16. Genomic imprinting
 The differential expression of genetic material, at
either chromosomal or allelic level, depending on
whether the genetic material has come from the
male or female parent
 Genomic imprinting is an epigenetic process
 genomic imprinting alters gene expression without
altering DNA sequence

17.  The first description of the imprinting phenomenon was
given by McGrath and Solter in 1984
 An epigenetic form of gene regulation that results in only
the copy inherited from father or mother to function
 Epigenetic modifiers of gene expression such as DNA
methylation, histone modification, non-RNA and higher-
order chromatin formation

18. Conclusion
 Histone proteins are most important for
packaging and ordering of DNA
 Modifications to histone proteins as a mechanism
of genome imprinting cause epigenetic changes
in the expression of phenotype
 But they do not alter the genetic constitution