Chromatin Architectures and Hox Gene Collinearity - Current Topics in Developmental Biology - page 119

A

Temporal colinearity

Repressive influence (temporal)

Activating influence (temporal)

Hoxd13 Hoxd12 Hoxd11 Hoxd10 Hoxd9 Hoxd8 Hoxd4 Hoxd3 Hoxd1

5 ¢ 3 ¢

B

Spatial colinearity

Hoxd4 Hoxd3 Hoxd1

Hoxd13 Hoxd12 Hoxd11 Hoxd10 Hoxd9 Hoxd8

5 ¢ 3 ¢

C

Quantitative colinearity

Mouse embryonic digits

Activating influence (spatial)

100%

Hoxd13 Hoxd12 Hoxd11 Hoxd10 Hoxd9 Hoxd8

5 ¢ 3 ¢

50%

0%

E12.5

Figure 4.4 Examples of collinear programs at the mouse HoxD cluster. (A) Directional
regulatory influences modulating temporal collinearity in the early embryonic trunk.
(B) Examples of local regulatory influences maintaining transcriptional states during
spatial collinearity in the embryonic trunk, at later stages. (C) Distant 5 0 -located
enhancers, imposing quantitative collinear expression of Hoxd genes in embryonic
digits. The resulting expression domains are indicated on the left and the quantitation
of steady-state mRNA levels in digits on the right. Panels (A and B) and (C) data are taken
from Tschopp et al. (2009) and Montavon, Le Garrec, Kerszberg, and Duboule (2008) .

Duboule, 2006; Zakany, Kmita, & Duboule, 2004 ). Activation of this phase
of transcription requires sequences located in the 3 0 neighborhood of the
gene cluster ( Spitz et al., 2001; Spitz, Herkenne, Morris, & Duboule,
2005 ). Subsequently, when digits are laid down, a quantitative collinear
mechanism is observed, which results in a progressive decrease in transcrip-
tional outcome, relative to genes' position ( Fig. 4.4 C). In developing digits,
Hoxd13 is expressed at maximum level, whereas Hoxd9 and Hoxd8 are tran-
scribed with minimal efficiency ( Kmita, Fraudeau, Herault, & Duboule,
2002; Montavon et al., 2008 ). In contrast to the early phase of activation,
this second mechanism requires sequences located in the 5 0 neighborhood
of the gene cluster ( Montavon et al., 2011; Spitz et al., 2005 ).