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Gata1 motif investing

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However, it is largely unknown how GATA1 properly organizes diversified gene expression to generate distinct expression profiles during erythropoiesis. Recent comprehensive analyses of GATA1 occupancy have shown that diversities in the neighboring sequence of consensus GATA-binding motifs can modify the transcriptional output. Multiple motifs of transcription regulation may act in a synergistic manner when they align in order with the GATA-binding motif in a cis-acting element.

In this article, we describe diverse DNA binding and transcriptional regulation mediated by GATA1 during erythropoiesis, focusing on the cis-acting element configuration. Consequently, the GATA1-centered transcriptional complex formation on the cis-acting elements is altered, which alters the transcriptional activity of GATA1. Transcription factors that interact with GATA1 have specific motifs that are enriched in repetitive regions of the genome. By contrast, SCL occupancy is abrogated by the lack of GATA1 on the E-box—GATA motif in certain genes, such as genes encoding erythroid-specific 5-aminolevulinate synthase, uroporphyrinogen III synthase, and pyruvate kinase, in which single-nucleotide mutations of the GATA motif have been found in patients with erythroid disorders Furthermore, the spacer lengths and sequences between E-box and GATA-binding motif vary at individual loci.

We envision delicate differences in sequence alignment among E-box—GATA composite elements conferring changes in complex structure, DNA-binding affinity, and protein—protein interactions, consequently diversifying target gene expression profiles. Many KLF1 variants have been found in recent years as the causes of different types of red cell disorders 52 , However, the number of co-occupied loci is lower than expected based on the significant cooperative function of GATA1 and KLF1 in the erythroid differentiation 56 , SP1, which has relatively ubiquitous expression pattern and plays key roles in critical biological process through regulating metabolic genes 58 , is reported to interact and cooperatively work with GATA1 to control gene expression 54 , KLF2 regulates embryonic erythropoiesis through redundantly and cooperatively working with KLF1 47 , Given that the sequence adjacent to the GATA-binding motif is varied in each region, individual GATA1 is predicted to access cis-regulatory regions differentially to contribute to gene expression and to allow sophisticated gene regulation.

However, the regulation of the spatiotemporal control of gene expression is poorly understood. The difference in orientation may influence GATA1 binding modes. There are three important observations about the N-finger function regarding its DNA binding. The R residue is located on the opposite face to the FOG1 association face To date, multiple substitution mutations in the NF have been found in inherited human diseases 24 , The disease pathogenesis caused by the R mutation likely differs from that due to impaired FOG1 association, although the disease phenotypes partially overlap 79 — GATA1-binding kinetics at conformation-specific binding sites.

GATA1 shows a dynamic expression profile during erythroid differentiation In mice and zebrafish, GATA1 dimerization is important for erythropoiesis because it regulates specific genes, including the Gata1 gene 18 , However, simple GATA1—DNA interactions only explain certain aspects of transcriptional regulation and fail to address comprehensive GATA1 regulation of various target genes, each of which has its own expression profile.

Recent findings have made great advances in our knowledge of how the molecules recruited to regions adjacent to GATA-binding motifs modify the binding kinetics, reaction stoichiometry, and complex formations centered with GATA1, which may allosterically regulate GATA1 transcriptional activity Figure 1.

The molecular mechanisms of GATA1 transcriptional activity have been dissected in recent decades, and the contributions of GATA1 mutations to disease pathogenesis have been vigorously investigated. Like Motif, Folio offers baskets of securities. At M1, investors trade baskets of securities called Pies. These are composed of stocks and ETFs.

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