Histone Chaperone HIRA in Regulation of Transcription Factor RUNX1

Majumder, Aditi; Syed, Khaja Mohieddin; Joseph, Sunu; Scambler, Peter J.; Dutta, Debasree

doi:10.1074/jbc.m114.615492

Cited by 24 publications

(48 citation statements)

References 36 publications

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“…HIRA also regulates expression of Runx1 itself by mediating H3.3 incorporation at the Runx1 promoter/enhancer region. HIRA is essential for Runx1 expression during the endothelial to hematopoietic transition (Majumder et al, 2015). Our microarray analysis showed expression of Runx1 to be higher at both 6 weeks and 6 months in Hira CKO skeletal muscle relative to control mice.…”

Section: Discussionmentioning

confidence: 88%

HIRA deficiency in muscle fibers causes hypertrophy and susceptibility to oxidative stress

Valenzuela

Soibam

et al. 2017

Journal of Cell Science

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Nucleosome assembly proceeds through DNA replication-coupled or replication-independent mechanisms. For skeletal myocytes, whose nuclei have permanently exited the cell cycle, replicationindependent assembly is the only mode available for chromatin remodeling. For this reason, any nucleosome composition alterations accompanying transcriptional responses to physiological signals must occur through a DNA replication-independent pathway. HIRA is the histone chaperone primarily responsible for replicationindependent incorporation of histone variant H3.3 across gene bodies and regulatory regions. Thus, HIRA would be expected to play an important role in epigenetically regulating myocyte gene expression. The objective of this study was to determine the consequence of eliminating HIRA from mouse skeletal myocytes. At 6 weeks of age, myofibers lacking HIRA showed no pathological abnormalities; however, genes involved in transcriptional regulation were downregulated. By 6 months of age, myofibers lacking HIRA exhibited hypertrophy, sarcolemmal perforation and oxidative damage. Genes involved in muscle growth and development were upregulated, but those associated with responses to cellular stresses were downregulated. These data suggest that elimination of HIRA produces a hypertrophic response in skeletal muscle and leaves myofibers susceptible to stress-induced degeneration.

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Section: Discussionmentioning

confidence: 88%

HIRA deficiency in muscle fibers causes hypertrophy and susceptibility to oxidative stress

Valenzuela

Soibam

et al. 2017

Journal of Cell Science

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“…Stable transfection using CaCl 2 was performed in HEK293T cells to produce lentiviral particles harboring shRNA against Aplf, as detailed in previous reports (Majumder et al, 2015). Another set of MEFs was transduced with lentiviral particles encoding the empty plko.1 vector and were treated as the control cells for the generation of iPSCs.…”

Section: Rna Interferencementioning

confidence: 99%

“…Immunostaining was performed as described previously (Majumder et al, 2015). Cells were incubated with primary antibodies overnight (see Tables S2, S4) and labeled with fluorescence-conjugated secondary antibodies (Alexa-Fluor-568, rabbit Alexa-Fluor-488 and mouse AlexaFluor-488).…”

Section: Immunofluorescencementioning

confidence: 99%

“…Cell pellets were suspended and lysed in RIPA buffer (10 mM Tris-HCl pH 7.6, 1% Triton X-100, 1% Nonidet P-40, 1% sodium deoxycholate, 0.1% SDS, 150 mM NaCl, 5 mM EDTA, 1 mM sodium orthovanadate, 1 mM PMSF and 10 mg/ml aprotinin), and the protein concentrations were determined by using the Bradford reagent (Bio-Rad; 500-0006) (Majumder et al, 2015), resolved on 10% or 12% SDS-PAGE gels. Antibodies used are listed in Tables S2, S4.…”

Section: Western Blottingmentioning

confidence: 99%

“…Histone metabolism is governed by histone chaperones (Avvakumov et al, 2011) such as Asf1a, Nap1, Caf1, which also assist in different nuclear processes including repair, replication, transcription and could modulate the post-translational modification of histones (Kim and Haber, 2009;Quivy et al, 2008;Sharma and Nyborg, 2008). They influence different processes during development (Dutta et al, 2010;Majumder et al, 2015) and disease (Corpet et al, 2011). However, the role of histone chaperones in the context of the induction of pluripotency is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Histone chaperone APLF regulates induction of pluripotency in murine fibroblasts

Syed¹,

Joseph²,

Mukherjee³

et al. 2017

Development

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The authors apologise to the readers for any confusion that this error might have caused. For the first time, we report here that the downregulation of histone chaperone Aprataxin PNK-like factor (APLF) promotes reprogramming by augmenting the expression of E-cadherin (Cdh1), which is implicated in the mesenchymal-to-epithelial transition (MET) involved in the generation of induced pluripotent stem cells (iPSCs) from mouse embryonic fibroblasts (MEFs). Downregulation of APLF in MEFs expedites the loss of the repressive MacroH2A.1 (encoded by H2afy) histone variant from the Cdh1 promoter and enhances the incorporation of active histone H3me2K4 marks at the promoters of the pluripotency genes Nanog and Klf4, thereby accelerating the process of cellular reprogramming and increasing the efficiency of iPSC generation. We demonstrate a new histone chaperone (APLF)-MET-histone modification cohort that functions in the induction of pluripotency in fibroblasts. This regulatory axis might provide new mechanistic insights into perspectives of epigenetic regulation involved in cancer metastasis.

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Molecular genetics of 22q11.2 deletion syndrome

Morrow

McDonald‐McGinn

Emanuel

et al. 2018

American J of Med Genetics Pt A

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103

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The 22q11.2 deletion syndrome (22q11.2DS) is a congenital malformation and neuropsychiatric disorder caused by meiotic chromosome rearrangements. One of the goals of this review is to summarize the current state of basic research studies of 22q11.2DS. It highlights efforts to understand the mechanisms responsible for the 22q11.2 deletion that occurs in meiosis. This mechanism involves the four sets of low copy repeats (LCR22) that are dispersed in the 22q11.2 region and the deletion is mediated by non-allelic homologous recombination events. This review also highlights selected genes mapping to the 22q11.2 region that may contribute to the typical clinical findings associated with the disorder and explain that mutations in genes on the remaining allele can uncover rare recessive conditions. Another important aspect of 22q11.2DS is the existence of phenotypic heterogeneity. While some patients are mildly affected, others have severe medical, cognitive and/or psychiatric challenges. Variability may be due in part to the presence of genetic modifiers. This review discusses current genome-wide efforts to identify such modifiers that could shed light on molecular pathways required for normal human development, cognition or behavior.

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Histone Chaperone HIRA in Regulation of Transcription Factor RUNX1

Cited by 24 publications

References 36 publications

HIRA deficiency in muscle fibers causes hypertrophy and susceptibility to oxidative stress

HIRA deficiency in muscle fibers causes hypertrophy and susceptibility to oxidative stress

Histone chaperone APLF regulates induction of pluripotency in murine fibroblasts

Molecular genetics of 22q11.2 deletion syndrome

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