Epigenetics of Reproduction in Animals - Building the Most Complex Structure on Earth - page 73

Bromo- and chromo-domain
binding proteins

Gene induction

AT Pase remodellers

HDACs, K9 HMTs

HATs, K4 HMTs

HP1
Me

HP1
Me

HP1
Me

HP1
Me

HP1
Me

Gene repression

Figure 2.6 The histone switch. Targeted modifications under the control of histone
methylases (HMTs), HATs, and HDACs alter the histone code at gene regulatory regions. This
establishes a structure that contains bromo- and chromo-domains that permits recruitment of
ATP-dependent chromatin remodeling factors to open promoters and allow further recruitment
of the basal transcription machinery. Deacetylation, frequently followed by histone
methylation, establishes a base for highly repressive structures, such as heterochromatin.
Acetylated histone tails are shown as brown stars. Methylation (Me) is shown to recruit
heterochromatin protein 1 (HP-1) ( Adcock et al., 2006 ).

Histone Modification and Chromatin Remodeling
A number of hormones such as thyroid hormone, retinoic acid, steroids like E2 and
testosterone, and other lipophilic hormones ( Sonoda et al., 2008 ) bind to nuclear
receptors, dissociating them from histone deacetylases (HDACs). The resulting
molecular complex recruits one or more of a family of about 300 coregulators (coac-
tivators and corepressors), including histone acetyltransferase (HAT). In this form,
the TF complex acetylates specific histones, thus remodeling chromatin, binding to
hormone specific response elements, and enabling transcription of specific genes
( Hinojos et al., 2005; Lonard and O'Malley, 2007 ) ( Figure 2.6 ). In the absence of
these nuclear hormones and other inducers, the nuclear receptors remain associated
with HDAC and prevent gene expression by compacting or “closing” chromatin
( Gamble and Freedman, 2002 ).
Protein hormones, which due to the larger molecular size cannot penetrate the cell
membrane, bind to the tramsmembrane portion of specific cell membrane receptors,
activating signal transduction pathways that end with histone acetylation/phospho-
rylation/chromatin remodeling and the expression of specific genes. So, for example,
the pituitary FSH binds its membrane receptor in ovarian granulosa cells, activating
a signal cascade that leads to phosphorylation and acetylation of histone H3 and to