A common cis-acting sequence in the DiGeorge critical region regulates bi-directional transcription of UFD1L and CDC45L

Mech Dev. 2001 Oct;108(1-2):81-92. doi: 10.1016/s0925-4773(01)00489-0.


Two to three megabase deletions on chromosome 22q11 are the cytogenetic findings most commonly associated with cardiac and craniofacial defects in humans. The constellation of clinical findings associated with these deletions is termed the 22q11 deletion syndrome. We had earlier described a patient with the 22q11 deletion phenotype who was hemizygous for an atypical 20 kb microdeletion in this region. The deletion included coding regions of two genes organized head-to-head, UFD1L and CDC45L, along with an 884 bp CpG-rich intervening region. Based on this genomic organization, we hypothesized that both genes may be co-expressed and co-regulated by sequences within this region. We demonstrate that expression of both genes is enhanced in a similar pattern in precursors of structures affected by the deletion. The intergenic region is sufficient to direct transcription most strongly in the developing pharyngeal arches and limb buds of transgenic mice and can also direct bi-directional transcriptional activation in a neural crest-derived cell line. Deletion analyses revealed that a 404 bp fragment closest to UFD1L is necessary and sufficient to direct this bi-directional transcriptional activity. These results reveal the presence of a conserved regulatory region in the 22q11 deletion locus that can direct simultaneous transcription of genes involved in ubiquitin mediated protein processing (UFD1L) and cell cycle control (CDC45L).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Base Sequence
  • Cell Cycle Proteins / genetics*
  • Cell Line
  • Chromosomes, Human, Pair 22 / genetics
  • Conserved Sequence
  • CpG Islands
  • DiGeorge Syndrome / genetics*
  • Gene Expression Regulation, Developmental
  • Humans
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Neural Crest / cytology
  • Neural Crest / metabolism
  • Phenotype
  • Proteins / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Deletion
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic


  • Adaptor Proteins, Vesicular Transport
  • CDC45 protein, human
  • Cdc45 protein, mouse
  • Cell Cycle Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • RNA, Messenger
  • UFD1 protein, human
  • Ufd1 protein, mouse