A complex array of different modes of regulation governs the precise Hox expression. Regulation primarily occurs at the transcriptional level via the combinatorial interplay of several signaling pathways and transcriptional factors that interact with positive and negative cis-acting sequences to differentially control Hox expression in a spatio-temporal and tissue-specific fashion. The proximity of Hox genes in clusters implies the integrated regulation of adjacent Hox promoters through the sharing, the competition and/or the selective use of Nitrofural defined enhancers. In parallel, global regulatory elements located outside the Hox clusters and able of long-distance action coordinate the expression of several genes along the Hox complexes. Large-scale chromatin remodeling events also participate to the regulation of the collinear expression of Hox genes. Transcriptional regulators of Hox gene expression have been identified. They include developmentally regulated factors like the CDX homeodomain-containing proteins that integrate retinoic acid, FGF and Wnt signaling for the setting of the correct expression domain of Hox genes. Hox genes are also directly responsive to RA, which activates retinoic acid receptors that then interact with retinoic acid GBR-12935 response elements identified near Hox genes mainly from paralog groups 1 to 5. Hox expression is under the control of HOX proteins themselves involved in auto- and cross-regulation. Finally, ubiquitously expressed transcription factors such as the multifunctional Yin Yang 1 protein can modulate Hox expression in specific contexts. A complex organization of overlapping transcriptional units encompassing the Hoxa5 locus exists, which results from alternative splicing and the use of three promoters, one proximal producing the 1.8-kb transcript and two distal ones giving rise to long noncoding RNAs. Using a transgenic approach, we have identified regulatory elements directing the developmental expression of the Hoxa5 proximal promoter.An 11.1-kb genomic fragment can recapitulate the temporal expression and substantially reconstitute the spatial pattern of the 1.8-kb Hoxa5 transcript in mouse embryos.