A Novel KRAB Domain-containing Zinc Finger Transcription Factor ZNF431 Directly Represses Patched1 Transcription

He, Zhenhua; Cai, Jing; Lim, Jong Won; Kroll, Kristen L.; Ma, Liang

doi:10.1074/jbc.m110.178780

Cited by 14 publications

(13 citation statements)

References 39 publications

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“…These transcription factors are involved in the regulation of cell differentiation, proliferation, apoptosis and neoplastic transformation[47–49]. A recent report implicates ZNF431 in controlling both Ptch1 basal expression and cellular response to Hedgehog signaling, which suggests a role for this transcription factor during developmental stages[50]. …”

Section: Discussionmentioning

confidence: 99%

GWAS reveals new recessive loci associated with non-syndromic facial clefting

Camargo

Rivera

Moreno

et al. 2012

European Journal of Medical Genetics

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We have applied a GWAS to 40 consanguineous families segregating cases of non-syndromic cleft lip with or without cleft palate (NS CL/P) (a total of 160 affected and unaffected individuals) in order to trace potential recessive loci that confer susceptibility to this common facial malformation. Pedigree-based association test (PBAT) analyses reported nominal evidence of association and linkage over SNP markers located at 11q25 (rs4937877, P = 2.7 × 10−6), 19p12 (rs4324267, P = 1.6 × 10−5), 5q14.1 (rs4588572, P-value = 3.36 × 10−5), and 15q21.1 (rs4774497, P = 1.08 × 10−4). Using the Versatile Gene-Based Association Study to complement the PBAT results, we found clusters of markers located at chromosomes 19p12, 11q25, and 8p23.2 overcome the threshold for GWAS significance (P < 1 × 10−7). From this study, new recessive loci implicated in NS CL/P include: B3GAT1, GLB1L2, ZNF431, ZNF714, and CSMD1, even though the functional association with the genesis of NS CL/P remains to be elucidated. These results emphasize the importance of using homogeneous populations, phenotypes, and family structures for GWAS combined with gene-based association analyses, and should encourage. other researchers to evaluate these genes on independent patient samples affected by NS CL/P.

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Section: Discussionmentioning

confidence: 99%

GWAS reveals new recessive loci associated with non-syndromic facial clefting

Camargo

Rivera

Moreno

et al. 2012

European Journal of Medical Genetics

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“…It is thought that KRAB-ZFPs bind to DNA and recruit corepressors such as KAP1, HDACs, HP1, and Setdb1 to silence gene expression from target promoters (Urrutia 2003). Recently, it has been shown that ZNF431 (the human homolog of Zfp431) directly represses expression of Patched 1, a target of Hh signaling (He et al 2011). It can be anticipated that Zfp157 modulates the expression of Stat6 and Gata-3 target genes in the subpopulation of alveolar cells in which these transcription factors are expressed.…”

Section: Zfp157 Is a Member Of A Family Of Transcriptional Repressorsmentioning

confidence: 99%

The Stat6-regulated KRAB domain zinc finger protein Zfp157 regulates the balance of lineages in mammary glands and compensates for loss of Gata-3

Oliver¹,

Khaled²,

Frend³

et al. 2012

Genes Dev.

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Lineage commitment studies in mammary glands have focused on identifying cell populations that display stem or progenitor properties. However, the mechanisms that control cell fate have been incompletely explored. Herein we show that zinc finger protein 157 (Zfp157) is required to establish the balance between luminal alveolar pStat5-and Gata-3-expressing cells in the murine mammary gland. Using mice in which the zfp157 gene was disrupted, we found that alveologenesis was accelerated concomitantly with a dramatic skewing of the proportion of pStat5-expressing cells relative to Gata-3 + cells. This suppression of the Gata-3 + lineage was associated with increased expression of the inhibitor of helix-loop-helix protein Id2. Surprisingly, Gata-3 becomes dispensable in the absence of Zfp157, as mice deficient for both Zfp157 and Gata-3 lactate normally, although the glands display a mild epithelial dysplasia. These data suggest that the luminal alveolar compartment of the mammary gland is comprised of a number of distinct cell populations that, although interdependant, exhibit considerable cell fate plasticity.

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“…C and 2D ), we found several genes coding for zinc finger proteins such as ZNF92 , ZNF107 and ZNF430 , not previously reported as being affected in the context of PMF. Moreover, HMGXB4 and ZNF431 , negative regulators of WNT and Hedgehog (Hh) pathways, respectively, were also found in the deleted signature. Finally, worth of notice is YTHDC1 , a splicing factor whose loss has been recently associated with poor overall and disease‐specific survival in endometrial cancer .…”

Section: Resultsmentioning

confidence: 99%

Integrative analysis of copy number and gene expression data suggests novel pathogenetic mechanisms in primary myelofibrosis

Salati

Zini

Nuzzo

et al. 2015

Intl Journal of Cancer

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Primary myelofibrosis (PMF) is a Myeloproliferative Neoplasm (MPN) characterized by megakaryocyte hyperplasia, progressive bone marrow fibrosis, extramedullary hematopoiesis and transformation to Acute Myeloid Leukemia (AML). A number of phenotypic driver (JAK2, CALR, MPL) and additional subclonal mutations have been described in PMF, pointing to a complex genomic landscape. To discover novel genomic lesions that can contribute to disease phenotype and/or development, gene expression and copy number signals were integrated and several genomic abnormalities leading to a concordant alteration in gene expression levels were identified. In particular, copy number gain in the polyamine oxidase (PAOX) gene locus was accompanied by a coordinated transcriptional up-regulation in PMF patients. PAOX inhibition resulted in rapid cell death of PMF progenitor cells, while sparing normal cells, suggesting that PAOX inhibition could represent a therapeutic strategy to selectively target PMF cells without affecting normal hematopoietic cells' survival. Moreover, copy number loss in the chromatin modifier HMGXB4 gene correlates with a concomitant transcriptional down-regulation in PMF patients. Interestingly, silencing of HMGXB4 induces megakaryocyte differentiation, while inhibiting erythroid development, in human hematopoietic stem/progenitor cells. These results highlight a previously un-reported, yet potentially interesting role of HMGXB4 in the hematopoietic system and suggest that genomic and transcriptional imbalances of HMGXB4 could contribute to the aberrant expansion of the megakaryocytic lineage that characterizes PMF patients.Myeloproliferative neoplasms (MPNs), that include Polycytemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are clonal hematopoietic stem cell disorders characterized by increased proliferation of terminally differentiated myeloid cells. In 2005, the JAK2V617F mutation was found to be present in almost all patients with PV, and in 60% of those with ET and PMF. 1 In addition, somatic mutations of JAK2 exon 12 are found in approximately 50% of JAK2V617F negative PV and activating mutations of the thrombopoietin receptor gene MPL are present in 5-10% of JAK2 negative ET or PMF. 2 Other mutations in several epigenetic modifiers, such as ASXL1, DNMT3a,

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A Novel KRAB Domain-containing Zinc Finger Transcription Factor ZNF431 Directly Represses Patched1 Transcription

Cited by 14 publications

References 39 publications

GWAS reveals new recessive loci associated with non-syndromic facial clefting

GWAS reveals new recessive loci associated with non-syndromic facial clefting

The Stat6-regulated KRAB domain zinc finger protein Zfp157 regulates the balance of lineages in mammary glands and compensates for loss of Gata-3

Integrative analysis of copy number and gene expression data suggests novel pathogenetic mechanisms in primary myelofibrosis

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