Understanding Histones: Structure, Function, and Modifications

in this video we'll talk about histones histones are highly basic proteins enriched in lysine and Arginine histones

can be found in eukaryotic cell nucleus histone forms the nucleosome it interacts with the DNA to form

functional unit of the chromatin known as the nucleosome histone has positive charges and the DNA backbone has

negative charges due to phosphate group and they interact with each other via electrostatic interaction histone

structure is highly conserved there are four basic type of histones h2a 2B H3 and H4 in all of these cases one common

theme is the histone fold which is highly conserved across the histones and across different species

now the difference lies in the tail length so the n-terminal histone tail is a site for several modifications and the

tail length is variable between different different histones and this is an extensive site for

different modifications like acetylation phosphorylation methylation ubiquity inhalation just to name a few

but question is how these modifications take place so obviously there are some proteins or machineries which can give

rise to these modifications and the second thing is what is the consequence of histone modification

now let me tell you there are several histone modifications which can change the accessibility of Chromatin towards

any other transcription Factor so it for example there are enzymes like histone acetyl transferase which can transfer

acetyl group onto the n-terminal of histones but the question is what is the

consequence now there is a phosphate backbone of DNA

which is tightly wrapped around the histone due to the positive charge of the lysine or Arginine group now when in

this particular region acetylation take place the positive charge gets masked that

means the interaction becomes weaker and the DNA now would be Loosely wrapped around the histone core

this would make the DNA accessible in this particular region from a context of transcription this makes sense because

many other proteins transcription Factor now gain the access to the region of this DNA

so overall accessibility can be increased by modifications like acetylation but acetylation is not the

only modification that takes place in the histone there are many other modifications

just to give you some idea that there are these acetylation can take place in different different residues for example

H4 lysine 8 or 16 acetylation is associated with the start site of gene expression

also there are many as other acetylation such as H4 lysine 5 or 12 acetylation marks the newly synthesized H4 so each

acetylation in different regions has their own sense majorly acetylated histones are

associated with euchromatin region a region of the chromatin which is highly active in terms of transcription whereas

deacetylated histone residues are found in heterochromatin which is transcriptionally silent

so acetylation of histones lead to a specific code in the chromatin which is read by specific barcode reader-like

molecules these barcode reader-like molecules are basically specific proteins which can recognize acetylated

histone so the question is who writes the code who reads the code and how I mean who can erase the code so the

writer of the code was basically the hat or histone acetyl transfer is the Eraser of this code was histone

de-acetylase and this code has a differential meaning now

the level of complexity in the histone code is brought about by different type of histone modifications so if we think

about euchromatin region there could be different modifications like acetylation and these acetylation can occur in

different different residues along with acetylation you can also have methylation in euchromatin region but

these methylations are brought the h3k4 dimethylation or h3k36 trimethylation there are phosphorylation which can also

be associated with active euchromatin there are specific modifications in heterochromatic region several

methylations like h3k27 methylation h3k9-dimethylation h3k9 trimethylations are associated with heterochromatic so

overall there could be different different types of modifications in the histones and each of these histone

modifications would be read as a combinatorial code now there are other histone variants but

before that let me tell you that there is one important part which is known as Linker histone shown here in brown and

it kind of work like a clip holding the DNA wrapped around the histone even tighter now there are different histone

variants such as let's say histone variant h2a z h 3.3 or heterogromatin Associated variant like simp a or macro

h2a some histone variants like gamma h2x is associated with double stranded DNA break so these are having this kind of

histone variants have different meaning now as per summary we looked at the histones are highly conserved and they

have lysine and Arginine residues which are site for several modifications like acetylation phosphorylation methylation

Etc histones are found in all eukaryotes across the species and highly conserved the structure of histone is the

structure of histone is conserved it contains that basic histone fold but in terminal tilts are aside for

modifications now different histone variants can change the chromatin architecture thereby changing chromatin

accessibility and overall it might have a role in changing the way of transcription

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