The Hematopoietic Stem and Progenitor Cell Cistrome

Hewitt, Kyle J.; Johnson, Kirby D.; Gào, Xin; Keleş, Sündüz; Bresnick, Emery H.

doi:10.1016/bs.ctdb.2016.01.002

Cited by 22 publications

(15 citation statements)

References 208 publications

(257 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, upon interacting with SCL, LMO2 released new hydrogen bonds in the SCL:E47 heterodimer that strengthened heterodimerization but also induced rotation in E47 (Omari et al 2013). The rotation in E47 altered the binding site preference for the ternary complex to such a degree that much of the complex site preference was contributed by another factor, named GATA-1 (Omari et al 2013;Hewitt et al 2016). This is a cardinal finding, since it shows at the atomic level how HLH proteins have the ability to select their target sites with great precision.…”

Section: Hlh Proteins In Hematopoiesismentioning

confidence: 99%

Helix–loop–helix proteins and the advent of cellular diversity: 30 years of discovery

Murre

2019

Genes Dev.

112

View full text Add to dashboard Cite

Helix-loop-helix (HLH) proteins are dimeric transcription factors that control lineage-and developmental-specific gene programs. Genes encoding for HLH proteins arose in unicellular organisms >600 million years ago and then duplicated and diversified from ancestral genes across the metazoan and plant kingdoms to establish multicellularity. Hundreds of HLH proteins have been identified with diverse functions in a wide variety of cell types. HLH proteins orchestrate lineage specification, commitment, self-renewal, proliferation, differentiation, and homing. HLH proteins also regulate circadian clocks, protect against hypoxic stress, promote antigen receptor locus assembly, and program transdifferentiation. HLH proteins deposit or erase epigenetic marks, activate noncoding transcription, and sequester chromatin remodelers across the chromatin landscape to dictate enhancer-promoter communication and somatic recombination. Here the evolution of HLH genes, the structures of HLH domains, and the elaborate activities of HLH proteins in multicellular life are discussed. Corresponding

show abstract

Section: Hlh Proteins In Hematopoiesismentioning

confidence: 99%

Helix–loop–helix proteins and the advent of cellular diversity: 30 years of discovery

Murre

2019

Genes Dev.

112

View full text Add to dashboard Cite

show abstract

“…By contrast, major progress has been made in understanding the mechanisms that control Kit expression. GATA2, which is expressed prior to GATA1 in HSPCs and in early erythroid precursors (Leonard et al, 1993;Weiss et al, 1994), directly activates Kit transcription (Gao et al, 2013;Jing et al, 2008;Lecuyer et al, 2002) and, as is often the case with GATA2, functions at chromatin sites with the basic helix-loop-helix transcription factor stem cell leukemia (Scl)/T-cell acute lymphocytic leukemia 1 (TAL1) and its associated factors, including the LIM domain proteins Ldb1 and Lmo2 (Hewitt et al, 2016;Hoang et al, 2016;Lecuyer et al, 2002;Wadman et al, 1997;Wozniak et al, 2008) (Fig. 2).…”

Section: Stem Cell Factor Synthesis and Mechanisms Of Actionmentioning

confidence: 99%

“…Other stress erythropoiesis circuits: deciphering the GATA factorregulated transcriptome A recent genomic analysis of cis-regulatory elements resembling the +9.5 enhancer mediating GATA2 function at the Gata2 locus has described new components of the GATA2-regulated HSPC cistrome (Hewitt et al, 2016(Hewitt et al, , 2015. A subset of these cis-elements constitutes GATA2-and anemia-activated (G2A) enhancers (Hewitt et al, 2017).…”

Section: Stem Cell Factor Synthesis and Mechanisms Of Actionmentioning

confidence: 99%

Mechanisms of erythrocyte development and regeneration: implications for regenerative medicine and beyond

et al. 2018

View full text Add to dashboard Cite

Hemoglobin-expressing erythrocytes (red blood cells) act as fundamental metabolic regulators by providing oxygen to cells and tissues throughout the body. Whereas the vital requirement for oxygen to support metabolically active cells and tissues is well established, almost nothing is known regarding how erythrocyte development and function impact regeneration. Furthermore, many questions remain unanswered relating to how insults to hematopoietic stem/progenitor cells and erythrocytes can trigger a massive regenerative process termed 'stress erythropoiesis' to produce billions of erythrocytes. Here, we review the cellular and molecular mechanisms governing erythrocyte development and regeneration, and discuss the potential links between these events and other regenerative processes.

show abstract

“…The intronic Samd14-Enh site harbors a composite E-box-GATA element (Hewitt et al, 2016; Hoang et al, 2016; Wadman et al, 1997) resembling the +9.5 site that increases Gata2 expression in hemogenic endothelium and triggers HSPC genesis in the mouse embryo (Gao et al, 2013). Genome editing revealed that Samd14-Enh increases Samd14 transcription in G1E cells (Hewitt et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

“…The E-box-GATA composite element at Samd14-Enh nucleates a multi-protein complex comprised of GATA-1/2, Scl/TAL1, LDB1 and LMO2 to mediate transcription of hematopoietic loci (Hewitt et al, 2016). In CD71 + Ter119 - splenic erythroid precursors, anemia upregulates Gata1, Gata2, Tal1, Lmo2 and Ldb1 , expression (Figure 4D, 4E, 4G, S6A).…”

Section: Resultsmentioning

confidence: 99%

GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia

et al. 2017

View full text Add to dashboard Cite

SUMMARY An enhancer with amalgamated E-box and GATA motifs (+9.5) controls expression of the regulator of hematopoiesis GATA-2. While similar GATA-2-occupied elements are common in the genome, occupancy does not predict function, and GATA-2-dependent genetic networks are incompletely defined. A “+9.5-like” element resides in an intron of Samd14 (Samd14-Enh) encoding a sterile alpha motif (SAM) domain protein. Deletion of Samd14-Enh in mice strongly decreased Samd14 expression in bone marrow and spleen. Although steady-state hematopoiesis was normal, Samd14-Enh-/- mice died in response to severe anemia. Samd14-Enh stimulated Stem Cell Factor/c-Kit signaling, which promotes erythrocyte regeneration. Anemia activated Samd14-Enh by inducing enhancer components and enhancer chromatin accessibility. Thus, a GATA-2/anemia-regulated enhancer controls expression of a SAM domain protein that confers survival in anemia. We propose that Samd14-Enh and an ensemble of anemia-responsive enhancers are essential for erythrocyte regeneration in stress erythropoiesis, a vital process in pathologies including β-thalassemia, myelodysplastic syndrome and viral infection.

show abstract

The Hematopoietic Stem and Progenitor Cell Cistrome

Cited by 22 publications

References 208 publications

Helix–loop–helix proteins and the advent of cellular diversity: 30 years of discovery

Helix–loop–helix proteins and the advent of cellular diversity: 30 years of discovery

Mechanisms of erythrocyte development and regeneration: implications for regenerative medicine and beyond

GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia

Contact Info

Product

Resources

About