HMG box gene transcriptions

File:Large lymphocytes-9.JPG

This is a large lymphocyte. Credit: Guy Waterval.{{free media}}

"Upstream Binding Factor (UBF) is important for activation of ribosomal RNA transcription and belongs to a family of proteins containing nucleic acid binding domains, termed HMG-boxes, with similarity to High Mobility Group (HMG) chromosomal proteins."

Chromosomal proteins

"Most HMG box proteins contain two or more HMG boxes and appear to bind DNA in a relatively sequence-aspecific manner (5, 13, 15, 16 and references therein). [...] they all appear to bind to the minor groove of the A/T A/T C A A A G-motif (10, 14, 18-20)."

"Previous studies in lymphocytes have described two DNA-binding HMG box proteins, TCF-1 and LEF-1, with affinity for the A/TA/TCAAAG motif found in several T cell-specific enhancers."

"The high mobility group-1 (HMG) box was originaly identified by Tjian and co-workers in the transcription factor UBF as a region of homology to HMG-1 proteins (Jantzen et al., 1990). UBF reportedly contained four such regions of -80 amino acids; one of these boxes was shown to mediate DNA binding."

"Interestingly, the sequence-specific HMG boxes characterized to date display high afinity to the A/TA/TCAAAG motif despite a low level of amino acid homology (typically <25% identity)."

"Human LEF-1 was originally identified as a T cell-specific protein binding to the TTCAAAG motif in the TCR-α enhancer (Waterman et al., 1991)."

"As analysed by gel retardation, the Sox-4 HMG box indeed bound to the AACAAAG motif (probe MWε-1; Figure 2B, lane 1). As described for other HMG boxes, Sox-4 interacted with DNA bases within the minor groove: substitution of A/T pairs for I/C pairs, which leaves the surface of the minor groove intact (Star and Hawley, 1991), had no apparent effect on binding affinity (lanes 2 and 4)."

Consensus sequences

"In mammals, the Tcf/Lef family consists of four genes: Tcf‐1, Lef‐1, Tcf‐3 and Tcf‐4. All TCF/LEF proteins display several common structural features (48,49). They contain a nearly identical DNA‐binding domain, the HMG box, recognizing the consensus sequence A/T A/T CAAA."

High mobility group proteins

Gene ID: 6932 is TCF7 transcription factor 7 on 5q31.1: "This gene encodes a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators. This gene is expressed predominantly in T-cells and plays a critical role in natural killer cell and innate lymphoid cell development. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/beta-catenin signaling pathway. Mice with a knockout of this gene are viable and fertile, but display a block in T-lymphocyte differentiation. Alternative splicing results in multiple transcript variants. Naturally-occurring isoforms lacking the N-terminal beta-catenin interaction domain may act as dominant negative regulators of Wnt signaling."

1. NP_001128323.2 transcription factor 7 isoform 3: "Transcript Variant: This variant (3, also known as A), differs in the 5' UTR, has multiple coding region differences, uses a downstream start codon, and differs in the 3' UTR, compared to variant 1. The resulting isoform (3) is shorter at the N-terminus and has a distinct C-terminus, compared to isoform 1."
2. NP_001333354.1 transcription factor 7 isoform 5: "Transcript Variant: This variant (8) contains an alternate exon in the coding region, compared to variant 1. The resulting isoform (5) is longer, compared to isoform 1."
3. NP_001333379.1 transcription factor 7 isoform 7: "Transcript Variant: This variant (9) differs in the 5' UTR, has multiple coding region differences, and uses a downstream start codon, compared to variant 1. The resulting isoform (7) is shorter at the N-terminus and has a distinct C-terminus, compared to isoform 1."
4. NP_001353431.1 transcription factor 7 isoform 8 [variant 10].
5. NP_003193.2 transcription factor 7 isoform 1: "Transcript Variant: This variant (1) encodes isoform (1)."
6. NP_963963.1 transcription factor 7 isoform 2: "Transcript Variant: This variant (2, also known as B), differs in the 5' UTR, has multiple coding region differences, and uses a downstream start codon, compared to variant 1. The resulting isoform (2) is shorter at the N-terminus, compared to isoform 1. Both variants 2 and 5 encode the same isoform."
7. NP_963965.1 transcription factor 7 isoform 4: "Transcript Variant: This variant (4, also known as C), differs in the 5' UTR, has multiple coding region differences, uses a downstream start codon, and differs in the 3' UTR, compared to variant 1. The resulting isoform (4) is shorter at the N-terminus and has a distinct C-terminus, compared to isoform 1."
8. NP_998813.1 transcription factor 7 isoform 2: "Transcript Variant: This variant (5) differs in the 5' UTR, has multiple coding region differences, and uses a downstream start codon, compared to variant 1. The resulting isoform (2) is shorter at the N-terminus, compared to isoform 1. Both variants 2 and 5 encode the same isoform."

Gene ID: 6934 is TCF7L2 transcription factor 7 like 2 on 10q25.2-q25.3: "This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms have been found for this gene."

1. NP_001139746.1 transcription factor 7-like 2 isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform."
2. NP_001124185.1 lymphoid enhancer-binding factor 1 isoform 2: "Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1. [...] SOX-TCF_HMG-box, class I member of the HMG-box superfamily of DNA-binding proteins. These proteins contain a single HMG box, and bind the minor groove of DNA in a highly sequence-specific manner. Members include SRY and its homologs in insects and vertebrates, and transcription factor-like proteins, TCF-1, -3, -4, and LEF-1. They appear to bind the minor groove of the A/T C A A A G/C-motif."
3. NP_001124186.1 lymphoid enhancer-binding factor 1 isoform 3: "Transcript Variant: This variant (3) lacks both an in-frame exon in the central coding region and an exon in the 3' coding region that causes a frameshift, compared to variant 1. The encoded isoform (3) has a distinct C-terminus and is shorter than isoform 1."
4. NP_001159591.1 lymphoid enhancer-binding factor 1 isoform 4: "Transcript Variant: This variant (4) differs in the 5' UTR and 5' coding region, and lacks an alternate in-frame exon in the central coding region, compared to variant 1. The encoded isoform (4) has a distinct N-terminus and is shorter than isoform 1."
5. NP_057353.1 lymphoid enhancer-binding factor 1 isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."

See also

• GA responsive complex gene transcription laboratory