Living and Adapting to Its Own Habitat - Building the Most Complex Structure on Earth - page 204

Nuclear membrane
Chromatin
fiber

Chromatin fiber
(30 nm dia.)

H1

Nucleosomes

H1

Nuclear
pore

DNA

Nuclear matrix

Figure 4.2 Modification of the histone components of nucleosomes helps regulate DNA
accessibility by promoting folding or unfolding of chromatin fibers and by recruiting
chromatin remodeling complexes and other factors to specific genomic loci.
Source : From Mizzen (2012) .

deacetylation of histones by histone methyltransferases (HMTs) and deacetylases
(HDACs), respectively. In euchromatin, genes are looser or “open,” hence accessible
to transcription factors, as a result of the action of histone acetylases (HATs), coacti-
vator complexes, and RNA polymerase. Reciprocal transition from heterochromatin
to euchromatin is presented in Figure 4.3 .
Epigenetic changes in histones occur in strictly determined sites of the DNA mol-
ecule, “where the organism needs them,” rather than in random places, clearly sug-
gesting that some form of information is used to produce these epigenetic marks. The
question is: are histones authentic generators of the information, or are they the convey-
ors of epigenetic information for gene expression coming from any upstream sources?
Now, there is adequate empirical evidence to answer the above question.
The source of information for histone acetylation, for example, is determined
conveniently in the case of nuclear receptors (TRs) that mediate the transcriptional
action of steroid, retinoid, thyroid, and other lipophilic endocrine hormones as well
as vitamins, dietary lipids, and so on ( Sonoda et al., 2008 ).
Usually the hormone forms a complex with its receptor and recruits one or more
coregulators (coactivators or corepressors). In the case of the hormone estradiol, E2,
the estradiol receptor complex (E2-ER) migrates to the nucleus where it enables
acetylation and phosphorylation of itself and of histones, recruits its coactivators,