The Questions of Developmental Biology

zipper (bZip)
Zinc finger:
Standard WT1, Krüppel, Engrailed Kidney, gonad, and macrophage development;
Drosophila segmentation
Nuclear hormone Glucocorticoid receptor, estrogen receptor, Secondary sex determination; craniofacial
receptors testosterone receptor, retinoic acid receptors development; limb development
Sry-Sox Sry, SoxD, Sox2 Bend DNA; mammalian primary sex determination;
ectoderm differentiation
Transcription factors have three major domains. The first is a DNA-binding domain that
recognizes a particular DNA sequence. The second is a trans-activating domain that activates or
suppresses the transcription of the gene whose promoter or enhancer it has bound. Usually, this
trans-activating domain enables the transcription factor to interact with proteins involved in
binding RNA polymerase (such as TFIIB or TFIIE; see Sauer et al. 1995). In addition, there may
be a protein-protein interaction domain that allows the transcription factor's activity to be
modulated by TAFs or other transcription factors.
Examples of transcription factors: MITF and Pax6
As examples of transcription factors, we can look at the Pax6 and
microphthalmia proteins mentioned in Chapter 4. The microphthalmia
(MITF) protein is necessary for the production of pigment cells and their
pigments. There are three functionally important domains of the MITF
protein. First, MITF has a protein-protein interaction domain that enables
it to dimerize with another MITF protein (Ferré-D'Amaré et al. 1993).
This homodimer (two microphthalmia proteins bound together)
forms the functional protein that can bind to DNA and activate the
transcription of certain genes (Figure 5.8). The second region, the
DNA-binding domain, is close to the amino-terminal end of the
protein and contains numerous basic amino acids that make
contact with the DNA (Hemesath et al. 1994;
Steingrímsson et al. 1994). This assignment was
confirmed by the discovery of various human and
mouse mutations that map within the DNA-binding site
for MITF and prevent the attachment of the MITF
protein to the DNA. Sites for MITF binding have been
found in the promoter regions for three pigment-cellspecific
proteins of the tyrosinase family (Bentley et al.
1994; Yasumoto et al. 1997). Without MITF, these
proteins are not synthesized properly (Figure 5.9) and
the melanin pigment is not made. These promoters all
contain the same 11-base-pair sequence, including the
core sequence CATGTG.