fig1

Different E-box binding transcription factors, similar neuro-developmental defects: ZEB2 (Mowat-Wilson syndrome) and TCF4 (Pitt-Hopkins syndrome)

Figure 1. Schematic overview of ZEB2 and TCF4. (A) Representation of (human) ZEB2 gene exons/introns (top) and ZEB2 protein structure (bottom). The largest ex8 encodes for the largest protein segment (in mouse, this corresponds to ex7). NIM: NuRD-interacting motif; NZF and CZF: N- and C-terminal zinc finger clusters; SBD: Smad-binding domain; HD: homeodomain-like domain; CID: CtBP-interacting domain (see Ref.[8]). (B) TCF4 gene protein-coding exons (20 in total), the thereafter identified 3’ untranslated exon (ex21) and introns (topl), and TCF4 protein structure (bottom). For reasons of huge complexity, the numerous other identified 5’-non-coding exons and various TSSs (indicated minimally as …) are not included here. AD: Transcription activation domain; NLS: nuclear localization signal; CE: conserved element; RD: repression domain (sometimes indicated as Rep); bHLH: basic helix-loop-helix DNA-binding domain; NE: nuclear export signal. (C) Alternative TCF4 transcripts as determined for brain. Untranslated regions are not included in this drawing, so only the used protein-coding exons are drawn (in black), together with the one 3’-untranslated ex21 (in grey). On the left, the number/letter combinations indicate that these transcripts also contain brain-specific exons (of which the numbers are given) that are still incorporated in the transcripts, but not coding for protein in these cases, while the letters indicate different mapped splice sites. Names of the transcripts are indicated on the right. The brown arrowhead at the bottom of the panel indicates the region of alternative splicing resulting in a full-length or a so-called Δ variant. The orange arrow at the bottom indicates the location of the splicing causing the generation of the so-called - and + isoforms. The images in (B, C) are based on the original report[67] and inspired by reviews[9,113].

Rare Disease and Orphan Drugs Journal
ISSN 2771-2893 (Online)
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