Disease relevance of AT Rich Sequence

• Initiation of DNA replication at the Escherichia coli chromosomal origin, oriC, occurs through an ordered series of events that depend first on the binding of DnaA protein, the replication initiator, to DnaA box sequences within oriC followed by unwinding of an AT-rich region near the left border [1].
• We examined the bi-allelic polymorphism at - 174 in the promoter region and the polymorphism in the 3' flanking AT rich region of the interleukin-6 (IL-6) gene in Swedish patients with myasthenia gravis (MG) and ethnically matched healthy individuals [2].
• However, short AT-rich sequences are distributed among the DnaA boxes of Streptomyces oriC [3].

High impact information on AT Rich Sequence

• Missing nucleoside experiments showed that SATB1 selectively binds in a special AT-rich sequence context where one strand consists of mixed A's, T's, and C's, excluding G's (ATC sequences) [4].
• Deletion mutants indicate that multiple AT-rich sequences, if contained in a minimal approximately 350 bp MAR fragment, can lead to efficient binding of ARBP [5].
• These fragments do not result from bulk nucleosome phasing in vivo, but arise from micrococcal nuclease cleavages internal to the core particle, at roughly 10-base pair intervals and at AT-rich sequences [6].
• SATB1 ('special AT-rich sequence binding 1'), a protein found predominantly in thymocytes, regulates genes by folding chromatin into loop domains, tethering specialized DNA elements to an SATB1 network structure [7].
• Despite its clear preference for AT-rich sequences, TBP can mediate TFIIIB assembly at diverse DNA sequences, including stretches containing only G and C. However, a mutant TBP, m3, which recognizes TATAAA and TGTAAA and is active for Pol III transcription, utilizes other sequences only poorly [8].

Biological context of AT Rich Sequence

• Binding site selection using in vitro-synthesized proteins reveals that the ROR alpha 1 and ROR alpha 2 isoforms bind DNA as monomers to hormone response elements composed of a 6-bp AT-rich sequence preceding a half-site core motif PuGGTCA (RORE) [9].
• Using gel shift assays, we demonstrated that LMX1B bound to two AT-rich sequences in the promoter region of NPHS2, the gene encoding podocin [10].
• The transcription termination sequence is believed to be at or beyond an AT-rich sequence preceded by a GC-rich sequence located distal to the cysteine tRNA gene [11].
• In vitro, HMGI protein was able to displace histone H1 from the upstream AT-rich region of the wild-type promoter but not from the promoter carrying mutations on the upstream high-affinity HMGI binding site [12].
• LCR-regulated transgene expression levels depend on the Oct-1 site in the AT-rich region of beta -globin intron-2 [13].

Anatomical context of AT Rich Sequence

• We produced constructs containing most of the GM-CSF 3'-UTR (303 nucleotides, pRSV-CATgm) or the 3'-terminal AT-rich region (116 nucleotides, pRSV-CATau) and measured CAT enzyme activity and CAT mRNA after transient transfection into EL-4 and NIH 3T3 cells [14].
• Deletion analysis of the iNOS promoter/enhancer revealed that an AT-rich sequence (-61 to -54) downstream of the NF-kappaB site (-85 to -76) in the 5'-flanking sequence was important for iNOS induction by interleukin-1beta and endotoxin in vascular smooth muscle cells [15].
• The islet amyloid polypeptide (IAPP; amylin) gene, which is also expressed in limited tissues such as pancreatic beta- and delta-cells, contained similar AT-rich sequences in its regulatory sequences [16].
• Using electrophoretic mobility shift assay and solid-phase DNase I footprinting methods, we identified a small nuclear protein from K562 cells that binds specifically to the first AT-rich region flanking the hypersensitive site 2 core sequence of the human beta-globin gene locus control region [17].

Associations of AT Rich Sequence with chemical compounds

• Treatment of cells with distamycin selectively enhances cleavage at nucleosome linker sites of the SAR and satellite regions, suggesting that AT-rich sequences flanking cleavage sites may be involved in determining topoisomerase II activity in the cell [18].
• Distamycin A is a well known polyamide antibiotic that can bind in the minor groove of duplex DNA primarily at AT-rich sequences both as a monomer or as a side-by-side antiparallel dimer [19].
• Guanine at position 3 determines DnaA-ATP preference, and changing this base to thymine at both I sites allows DnaA-ADP to bind and open oriC, although DNA strand separation is not precisely localized in the AT-rich region [20].
• A factor present in nuclear extracts from endothelial and nonendothelial cells binds to an AT-rich sequence located between nt -133 and -125 [21].
• The AT-rich region often contained ATTTA motifs, 5'-AAT-3' or 5'-TAA-3' trinucleotides which were reported to be involved in rapidly degrading mRNA [22].

Gene context of AT Rich Sequence

• Surprisingly, we found that an AT-rich region 5' to the GC box also is important for MIG1 binding [23].
• A near homogeneous 20-kDa DNA-binding protein purified from rat brain was able to bind to these AT-rich regions of both Ng/RC3 and PKC-gamma genes with footprints containing ATTA, ATAA, and AATA sequences [24].
• Synergism between STAT3 or STAT3-C and c-Jun is impaired by mutation of the APRE (SIE) or either AP1 site, as well as by mutations that alter the AT-rich regions or their phasing [25].
• The binding of EGR1 to the GC-rich region prevented TBP binding to the AT-rich region [26].
• HMGA1 proteins belong to a family of nonhistone chromatin proteins able to bind DNA in AT-rich regions and to interact with various transcription factors thus enhancing or inhibiting gene transcription by acting as architectural proteins [27].

Analytical, diagnostic and therapeutic context of AT Rich Sequence

• In vitro footprinting and quantitative gel shift analyses showed that PF1 binds preferentially to the PE1 element but also at lower affinity to two other AT-rich regions upstream of PE1 [28].
• STS mapping narrowed the 1p21.2 breakpoint to a 1990 bp AT-rich region, and junction fragments were amplified by nested PCR [29].
• Primer extension, S1 nuclease protection, and genomic and cDNA sequence analysis demonstrate that gene transcripts are initiated within a conserved AT-rich sequence element immediately preceding the ATG translation initiation codon and the short 5' untranslated region is not extended by transsplicing [30].
• Isothermal titration calorimetry (ITC) profiles of berenil bound to different DNAs show that, despite the strong preference of berenil for AT-rich regions in DNA, it can bind to other DNA sequences significantly [31].

References