Interaction between the homeodomain protein HOXC13 and ETS family transcription factor PU.1 and its implication in the differentiation of murine erythroleukemia cells

Yamada, Toshiyuki; Shimizu, Takeshi; Suzuki, Motoo; Kihara-Negishi, Fumiko; Nanashima, Naoki; Sakurai, Takeshi; Yang, Fan; Akita, Miki; Oikawa, Tsuneyuki; Tsuchida, Shigeki

doi:10.1016/j.yexcr.2007.11.005

Cited by 10 publications

(10 citation statements)

References 36 publications

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“…42,44,45 Together, this suggests that Hoxa9 associates with enhanceosomes through homeodomain-mediated interactions, interactions with DNA binding affinity cofactors such as Meis1, and interactions with TFs that include C/EBP␣, CREB1, and STAT5.…”

Section: Hoxa9 Is Organized Into Enhanceosomes Containing Lineage-resmentioning

confidence: 99%

Identification and characterization of Hoxa9 binding sites in hematopoietic cells

Huang

Sitwala²,

Bronstein³

et al. 2012

Blood

173

194

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IntroductionHox proteins are homeodomain-containing transcription factors (TFs) that play a vital role in establishing body plan during development. In addition to this role in body planning, Hox proteins have been implicated in limb regeneration, wound healing, adipogenesis, and hematopoietic stem cell self-renewal. 1 Hoxa9, in particular, is expressed at high levels in early hematopoietic progenitor cells and promotes stem cell expansion. In contrast, Hoxa9 down-regulation is associated with hematopoietic differentiation. 2,3 In keeping with this role, Hoxa9 knock-out mice show defects in B and T-cell lymphopoiesis and myelopoiesis. 4 HOXA9 has been intensively studied because of its central role in human acute leukemias. [5][6][7][8] Early studies of BXH2 mice, which spontaneously develop acute myeloid leukemia (AML) as a result of endogenous retroviral integration, showed that overexpression of Hoxa9, as a result of integrations at the locus, is one of the most common genetic abnormalities in these leukemias. 9,10 Subsequent gene expression profiling studies showed that HOXA9 is expressed in many AMLs. Of 6817 genes tested, HOXA9 was the single most predictive marker for poor prognosis. 11 Certain subtypes of acute leukemias, particularly those with rearrangements of the mixed lineage leukemia (MLL) gene, show especially high expression of A cluster HOX genes, 5,6,8 which is critical for MLL fusion protein-mediated transformation. 12,13 However, deregulation of Hox expression also appears to play a central role in leukemias without MLL rearrangements, including AMLs associated with the CALM-AF10 translocation, fusions of HOXA9 to the nucleoporin gene NUP98 in a subset of leukemias with the t(7;11), 14,15 overexpression of CDX2 or CDX4 [16][17][18] and identified T-cell acute lymphoblastic leukemia cases with translocations between the TCR␤ and the HOXA9/HOXA10 locus. 19

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Section: Hoxa9 Is Organized Into Enhanceosomes Containing Lineage-resmentioning

confidence: 99%

Identification and characterization of Hoxa9 binding sites in hematopoietic cells

Huang

Sitwala²,

Bronstein³

et al. 2012

Blood

173

194

View full text Add to dashboard Cite

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“…The importance of these additional Ets interaction partners merits structural study, as some interfaces appear to be novel and even if such surfaces appear similar to those already characterized, subtle residue movements are key to co-operative binding on DNA [11,12]. Furthermore, many structurally uncharacterized Ets domain interactions involve other TFs central to cellular development or neoplasia, such as the androgen receptor [54], HOX homeodomains [55] and forkhead TFs, although an ETS1–FOXO1 (forkhead box O1) structure (PDB code 4LG0) is currently on hold in the PDB.…”

Section: Ets Domains As Protein–protein Interaction Modulesmentioning

confidence: 99%

Recent advances in the structural molecular biology of Ets transcription factors: interactions, interfaces and inhibition

Cooper

Newman

Gileadi

2014

Biochemical Society Transactions

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The Ets family of eukaryotic transcription factors is based around the conserved Ets DNA-binding domain. Although their DNA-binding selectivity is biochemically and structurally well characterized, structures of homodimeric and ternary complexes point to Ets domains functioning as versatile protein-interaction modules. In the present paper, we review the progress made over the last decade to elucidate the structural mechanisms involved in modulation of DNA binding and protein partner selection during dimerization. We see that Ets domains, although conserved around a core architecture, have evolved to utilize a variety of interaction surfaces and binding mechanisms, reflecting Ets domains as dynamic interfaces for both DNA and protein interaction. Furthermore, we discuss recent advances in drug development for inhibition of Ets factors, and the roles structural biology can play in their future.

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“…HOXC13 has also been found to be a fusion partner of NUP98 in adult acute myeloid leukemia [6,7]. This protein also binds to the ETS family transcription factor PU.1 and affects the differentiation of murine erythroleukemia [8]. Although HOX13 is critical player in hair development and disease, little is known about its own regulation.…”

Section: Introductionmentioning

confidence: 99%

Mixed lineage leukemia histone methylases play critical roles in estrogen‐mediated regulation of HOXC13

et al. 2009

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HOXC13, a homeobox‐containing gene, is involved in hair development and human leukemia. The regulatory mechanism that drives HOXC13 expression is mostly unknown. Our studies have demonstrated that HOXC13 is transcriptionally activated by the steroid hormone estrogen (17β‐estradiol; E2). The HOXC13 promoter contains several estrogen‐response elements (EREs), including ERE1 and ERE2, which are close to the transcription start site, and are associated with E2‐mediated activation of HOXC13. Knockdown of the estrogen receptors (ERs) ERα and ERβ suppressed E2‐mediated activation of HOXC13. Similarly, knockdown of mixed lineage leukemia histone methylase (MLL)3 suppressed E2‐induced activation of HOXC13. MLLs (MLL1–MLL4) were bound to the HOXC13 promoter in an E2‐dependent manner. Knockdown of either ERα or ERβ affected the E2‐dependent binding of MLLs (MLL1–MLL4) into HOXC13 EREs, suggesting critical roles of ERs in recruiting MLLs in the HOXC13 promoter. Overall, our studies have demonstrated that HOXC13 is transcriptionally regulated by E2 and MLLs, which, in coordination with ERα and ERβ, play critical roles in this process. Although MLLs are known to regulate HOX genes, the roles of MLLs in hormone‐mediated regulation of HOX genes are unknown. Herein, we have demonstrated that MLLs are critical players in E2‐dependent regulation of the HOX gene.

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Interaction between the homeodomain protein HOXC13 and ETS family transcription factor PU.1 and its implication in the differentiation of murine erythroleukemia cells

Cited by 10 publications

References 36 publications

Identification and characterization of Hoxa9 binding sites in hematopoietic cells

Identification and characterization of Hoxa9 binding sites in hematopoietic cells

Recent advances in the structural molecular biology of Ets transcription factors: interactions, interfaces and inhibition

Mixed lineage leukemia histone methylases play critical roles in estrogen‐mediated regulation of HOXC13

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