Sequence and functional analysis of an upstream regulatory region of human HOXA7 gene

Role of HOXA7 to HOXA13 and PBX1 genes in various forms of MRKH syndrome (congenital absence of uterus and vagina)

“…Although large-scale developmental signals deficiency would probably not account for restricted and non lethal malformations such as those observed for the MRKH syndrome, HOX misregulation due to mutations/deletions outside the coding regions could do it as already described in the HOXD gene cluster [ 47 ] and in HOXA13 gene promoter [ 48 ]. Some few regulatory regions have been characterized in the HOXA gene cluster among which, the so-called HCR (Human Control Region) [ 49 ] lying next to HOXA7, a gene somehow involved in Müllerian differentiation [ 15 ]. This 1.1 kb DNA sequence, as well as its conserved mouse equivalent, has been shown to set the anterior boundary of HOXA7 expression [ 49 ] and therefore putative other HOXA genes of the same cluster.…”

“…Some few regulatory regions have been characterized in the HOXA gene cluster among which, the so-called HCR (Human Control Region) [ 49 ] lying next to HOXA7, a gene somehow involved in Müllerian differentiation [ 15 ]. This 1.1 kb DNA sequence, as well as its conserved mouse equivalent, has been shown to set the anterior boundary of HOXA7 expression [ 49 ] and therefore putative other HOXA genes of the same cluster. Southern-blot experiments aiming at detecting length polymorphism such as deletion or duplication in the [HCR-HOXA7] area did not reveal any major genetic event in any of the patients investigated (results not shown).…”

The leukemogenic fusion of MLL with ENL creates a novel transcriptional transactivator

“…22 This promoter is conserved between human and mouse and the human promoter counterpart has been shown to be functional in transgenic mice. 23,24 We report here that the fusion of MLL and ENL creates a protein with new, unique transcriptional properties that strongly transactivated a variety of promoters. This activation was promoter as well as cell line specific and required the integrity of the MT region of MLL and the C-terminus of ENL.…”

“…A 480 bp enhancer and a transcription start site are the only regulatory elements that have been so far experimentally identified within the 2.8 kb Hoxa7 promoter sequence. 23,24 Additionally a multitude of potential transcription factor sites has been predicted downstream of the transcription start by computer programs. 29 Several truncated promoter mutants were inserted into the luciferase reporter pGL-3 basic and cotransfected into REH cells together with either empty expression vector or the MLL-ENL expression construct (Figure 2b).…”