Anilkumar C

PALM 3001

Histone Proteins and Genome

Imprinting

Now……..

1 • Histone proteins

2 • Classes of Histones

3 • Functions of histone proteins

4 • Histone modifications

5 • Genomic imprinting

6 • Mechanisms of imprinting

7 • Imprinting in plants

Introduction

Histone proteins: Histones are a special group of

proteins found in the nuclei of eukaryotic cells

responsible for DNA folding and chromatin

formation.

Chemically they are-

• highly alkaline basic proteins

• Histones are positively charged

• abundance of positive amino-acids, arginine and lysine

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 toform one octameric nucleosome core particle, and 147 basepairs of DNA wrap around this core particle.

contain more lysine

contain more arginine

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

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

Levels of chromatin structure

• Some histone proteins function as spools for the thread-like

DNA to wrap around

• looks like beads on a string

• The nucleosomes + H1 histones = 30 nm spiral

Solenoid

• it maintains the chromosomal

structure

Histone Modifications

• Each histone protein has a structured domain, ‘Histone

Fold’ and unstructured ‘N- terminal tail’

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

Histone Acetylation & Deacetylation

• Histone acetylation

• – Histone acetyl transferases (HATs)

• Adds acetyl groups to histone tails

• Reduces positive charge and weakens interaction of histoneswith DNA

• Facilitates transcription by making DNA more accessible toRNA polymerase II

• Histone deacetylation

• – Histone deacetylases (HDACs)

• Removes acetyl groups from histone tails

• Increases interaction of

DNA and histones

• Represses transcription

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.

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

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.

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

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

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

• 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

Mechanisms of Imprinting

DNA Methylation

Attachment of methyl (-CH3) groups to the bases of DNA.

Occurs at cytosine that follows guanine at CpG dinucleotides

Non-coding RNAs

A significant number of imprinted genes are transcribed

to give a non-coding RNA.

Non-coding RNAs include antisense transcript, small

nucleolar RNAs (Sno RNAs), micro RNAs, pseudo

genes and other RNA of unknown function

Histone modification & chromatin

remodeling

Histone modifiations includes Acacetylation of lysines

(HATs), Phosphorylation of serines (Kinases) and

Methylation of lysines

Methylation of lysine-4 in H3 is associated with active

genes and methylation of lysine-9 in H3 is associated with

inactive genes

The allele-specific gene silencing in H19 is in part

mediated by hypermethylation and histone deacetylation

Imprinted genes in plants

• A similar imprinting phenomenon has also been described

in flowering plants (angiosperms)

• imprinted genes are responsible for the triploid block effect

in flowering plants that prevents hybridization between

diploids and autotetraploids.

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