Heterochromatin without methylation

Graham Dellaire dellaire at odyssee.net
Mon Apr 7 20:52:44 EST 1997


Heterochromatin is a cytological description of chromatin in one sense
(i.e. stains under certain conditions, ex. with Giemsa)  and a genetic
description of a chromatin state, in another (i.e. late replicating and
or areas of repressed transcription).

To address your questions about lack of methylation in Drosophila at
CpG's I would like to bring up acetylation of histones, in particular
histone 4.

Hypoacetylation can be correlated with repressed transcription. ex. in
Tetrahymena, vegatatively growing cells of this species contain a
transcriptionally inactive micronucleus which is hypoacetylated and a
macronucleus which is transcriptionally active and hyperacetylated. 

Acetylation may serve as a target for proteins that open up chromatin
and thus make it accessible to transcription factors or may sterically
hinder the tight packing of histones with DNA in the  nucleosome
particle (i.e. fascilitating displacement by lower energy requirements
to remove histones).  I am not aware of changes in replication timing
based on acetylation... (anyone care to comment??)

Acetylation occurs in both vertebrates and invertebrates whereas I
believe methylation only occurs in vertebrates.  It seems to be a
relatively new mode of fixing transcription states, or as cell memory. 
And as for imprinting and perhaps heterochromatin itself methylation is
most likely an after effect do to some underlining process of
heterochromatization rather than a cause.  Methylation may therefore
exist as a mechanism of locking transcriptional repression, or
preventing leakiness of promoters, rather than strickly acting as the
primary mechanism of transcriptional repression.  Acetylation therefore
is a much older system of cell memory or imprinting to make sure open
regions of chromatin stay open for transcription.  This may be the case
in Drosophila... I don't know.  (anyone??)

I think DNA binding proteins may have a bigger affect on
heterochromatization of DNA than methylation or acetylation, although
they are perhaps intimately involved in there binding and inheritance of
this binding when chromatin is replicated.

Drosophila has some very interesting proteins with this respect, the
polycomb group of proteins (Pc-G).  Multimeric complexes containing the
Pc-G proteins are thought to induce heterochromatin-like structures,
which stably and heritably inactivate transcription.  One key
characteristic of the Pc-G proteins is the chromo-domain.
Heterochromatin Protein 1 (HP-1) from Drosophila contains a similar
domain called the chromo shadow domain. The Schizosaccharomyces pombe
SW16 protein, involved in repression of the silent mating-type loci, is
a member of the chromo shadow group like HP-1.  Chromo domain-containing
proteins can therefore be divided into two classes depending on the
presence, for example in HP1, or absence, for example in Pc, of the
chromo shadow domain.

Mechanisms of delaying replication timing are more complicated.  In
yeast I think there is some evidence that position to the telomere can
affect replication timing (Dan Gottschling's work, Fred Hutchinson
Center in Seattle). This could be as a result of telomere specific
proteins.... i.e. the spreading of heterochromatin and associated
proteins (like HP-1 or Pc-G proteins as in Drosophila PEV).

Just a few musings,

Hope this helps

Graham Dellaire

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