Navigating Transcriptional Coregulator Ensembles to Establish Genetic Networks

DeVilbiss, Andrew W.; Tanimura, Nobuyuki; McIver, Skye C; Katsumura, Koichi R.; Johnson, Kirby D.; Bresnick, Emery H.

doi:10.1016/bs.ctdb.2016.01.003

Cited by 19 publications

(20 citation statements)

References 250 publications

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“…Furthermore, GATA1 is essential to the development of the erythroid lineage and the regulation of RBC differentiation. 46,47 Specifically, the 2 erythroid-related GATA factors are 2 out of 6 GATA factors that are able to induce the greatest amount of transcriptional activity via the rs311103[G] segment ( Figure 5B). Nonetheless, the EMSA results using K-562 nuclear extracts, as well as the ChIP analysis, suggest that GATA1, but not GATA2, is involved in the differential transcriptional activity of the rs311103[G] and rs311103[C] segments.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, various transcription factors and cofactors have been shown to associate with the GATA1 and GATA2 factors and to be involved in the regulation of the activation/repression functions of GATA1/GATA2 with respect to erythroid gene expression. [46][47][48][49] Some of these factors have been identified as being capable of mediating long-range interactions between the enhancers and the promoters of erythroid genes. [50][51][52] Further studies are needed to delineate the molecular details associated with the allelic variation in expression of the XG and CD99 genes with respect to the rs311103[G] and rs311103 [C] alleles.…”

Section: Discussionmentioning

confidence: 99%

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The molecular genetic background leading to the formation of the human erythroid-specific Xga/CD99 blood groups

Yeh

Chang

Twu³

et al. 2018

Blood Advances

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The Xg and CD99 antigens of the human Xg blood group system show a unique and sex-specific phenotypic relationship. The phenotypic relationship is believed to result from transcriptional coregulation of the and genes, which span the pseudoautosomal boundary of the X and Y chromosomes. However, the molecular genetic background responsible for these blood groups has remained undetermined. During the present investigation, we initially conducted a pilot study aimed at individuals with different Xg/CD99 phenotypes; this used targeted next-generation sequencing of the genomic areas relevant to and This was followed by a large-scale association study that demonstrated a definite association between a single nucleotide polymorphism (SNP) rs311103 and the Xg/CD99 blood groups. The G and C genotypes of SNP rs311103 were associated with the Xg(a+)/CD99H and Xg(a-)/CD99L phenotypes, respectively. The rs311103 genomic region with the G genotype was found to have stronger transcription-enhancing activity by reporter assay, and this occurred specifically with erythroid-lineage cells. Such activity was absent when the same region with the C genotype was investigated. In silico analysis of the polymorphic rs311103 genomic regions revealed that a binding motif for members of the GATA transcription factor family was present in the rs311103[G] region. Follow-up investigations showed that the erythroid GATA1 factor is able to bind specifically to the rs311103[G] region and markedly stimulates the transcriptional activity of the rs311103[G] segment. The present findings identify the genetic basis of the erythroid-specific Xg/CD99 blood group phenotypes and reveal the molecular background of their formation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The molecular genetic background leading to the formation of the human erythroid-specific Xga/CD99 blood groups

Yeh

Chang

Twu³

et al. 2018

Blood Advances

View full text Add to dashboard Cite

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“…GATA-1-mediated replacement of GATA-2 represses Gata2 transcription during erythroid maturation via FOG-1-and SetD8-dependent mechanisms. 65 GATA switching occurs at 5 highly conserved Gata2 sites, 277, 23.9, 22.8, 21.8, and 19.5 kb relative to the 1S promoter. 28,56,57,64 As GATA-2 and GATA-1 occupy these sites at the active and repressed locus, respectively, predictions could not be made regarding whether sites contribute to Gata2 activation or repression or if they are dispensable.…”

Section: Gata2 Gata2mentioning

confidence: 99%

“…14, 64 GATA-1 and GATA-2 genomic occupancy sites and target genes can be cell type specific and/or overlapping. 18,49,51 The milieu of GATA factor-associated coregulators almost certainly contributes to the context dependence 65 (Figure 2B). The coregulator ensemble mediating GATA factor activity serves diverse functions, including catalysis of protein modifications (eg, acetylation, sumoylation, and phosphorylation) that directly or indirectly (via chromatin alterations) modulate GATA factor activity ( Figure 1A-B).…”

Section: Introductionmentioning

confidence: 97%

“…90 Another example of context-dependent regulation that impacts a subset of the GATA-1 target gene ensemble involves GATA-1 interactions with histone methyltransferases. 65 SetD8, the only known histone H4 K20 monomethyltransferase (H4K20me1), mediates GATA-1-dependent repression of select target genes. 91 SetD8 confers erythroblast survival, 92 which may or may not reflect its GATA-1 corepressor function.…”

Section: Introductionmentioning

confidence: 99%

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The GATA factor revolution in hematology

Katsumura

Bresnick

2017

Blood

127

145

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The discovery of the GATA binding protein (GATA factor) transcription factor family revolutionized hematology. Studies of GATA proteins have yielded vital contributions to our understanding of how hematopoietic stem and progenitor cells develop from precursors, how progenitors generate red blood cells, how hemoglobin synthesis is regulated, and the molecular underpinnings of nonmalignant and malignant hematologic disorders. This thrilling journey began with mechanistic studies on a β-globin enhancer- and promoter-binding factor, GATA-1, the founding member of the GATA family. This work ushered in the cloning of related proteins, GATA-2-6, with distinct and/or overlapping expression patterns. Herein, we discuss how the hematopoietic GATA factors (GATA-1-3) function via a battery of mechanistic permutations, which can be GATA factor subtype, cell type, and locus specific. Understanding this intriguing protein family requires consideration of how the mechanistic permutations are amalgamated into circuits to orchestrate processes of interest to the hematologist and more broadly.

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PI3k/AKT signaling pathway: Erythropoiesis and beyond

Jafari

Ghadami

Dadkhah

et al. 2018

Journal Cellular Physiology

232

142

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Erythropoiesis is a multi-step process that involves the differentiation of hematopoietic stem cells into mature red blood cells (RBCs). This process is regulated by several signaling pathways, transcription factors and microRNAs (miRNAs). Many studies have shown that dysregulation of this process can lead to hematologic disorders. PI3K/AKT is one of the most important pathways that control many cellular processes including, cell division, autophagy, survival, and differentiation. In this review, we focus on the role of PI3K/AKT pathway in erythropoiesis and discuss the function of some of the most important genes, transcription factors, and miRNAs that regulate different stages of erythropoiesis which play roles in differentiation and maturation of RBCs, prevention of apoptosis, and autophagy induction. Understanding the role of the PI3K pathway in erythropoiesis may provide new insights into diagnosing erythrocyte disorders.

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Navigating Transcriptional Coregulator Ensembles to Establish Genetic Networks

Cited by 19 publications

References 250 publications

The molecular genetic background leading to the formation of the human erythroid-specific Xga/CD99 blood groups

The molecular genetic background leading to the formation of the human erythroid-specific Xga/CD99 blood groups

The GATA factor revolution in hematology

PI3k/AKT signaling pathway: Erythropoiesis and beyond

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