Reciprocal regulation of Rag expression in thymocytes by the zinc-finger proteins, Zfp608 and Zfp609

Reed, Nykolaus P.; Henderson, Melodie A.; Oltz, Eugene M.; Aune, Thomas M.

doi:10.1038/gene.2012.47

Cited by 12 publications

(12 citation statements)

References 25 publications

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“…We show that in mice, the two Drosophila scribbler homologs Zfp608 and Zfp609 are expressed in the embryonic forebrain in a mutually exclusive manner, possibly through direct cross-repression, analogous to what was reported in developing thymocytes (Reed et al., 2013). Indeed, we find that Zfp609 and Nipbl bind to the Zfp608 promoter in NSCs to silence its transcription.…”

Section: Discussionsupporting

confidence: 82%

“…Zfp609 transcripts are enriched in and subsequently become restricted to the progenitor population as cortical neurogenesis peaks at E14.5. The absence of Zfp609 transcripts from cells in the SVZ/IZ at this stage could be attributed to direct repression by Zfp608, as occurs in developing thymocytes (Reed et al., 2013). At later stages of development, Zfp609 expression is detected in the neurons of the cortical plate (CP) and in stem cells near the ventricular surface.…”

Section: Resultsmentioning

confidence: 96%

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Nipbl Interacts with Zfp609 and the Integrator Complex to Regulate Cortical Neuron Migration

Berg

Azzarelli

Oishi

et al. 2017

Neuron

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SummaryMutations in NIPBL are the most frequent cause of Cornelia de Lange syndrome (CdLS), a developmental disorder encompassing several neurological defects, including intellectual disability and seizures. How NIPBL mutations affect brain development is not understood. Here we identify Nipbl as a functional interaction partner of the neural transcription factor Zfp609 in brain development. Depletion of Zfp609 or Nipbl from cortical neural progenitors in vivo is detrimental to neuronal migration. Zfp609 and Nipbl overlap at genomic binding sites independently of cohesin and regulate genes that control cortical neuron migration. We find that Zfp609 and Nipbl interact with the Integrator complex, which functions in RNA polymerase 2 pause release. Indeed, Zfp609 and Nipbl co-localize at gene promoters containing paused RNA polymerase 2, and Integrator similarly regulates neuronal migration. Our data provide a rationale and mechanistic insights for the role of Nipbl in the neurological defects associated with CdLS.

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Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 96%

Nipbl Interacts with Zfp609 and the Integrator Complex to Regulate Cortical Neuron Migration

Berg

Azzarelli

Oishi

et al. 2017

Neuron

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“…ZBTB10 is a POK transcriptional repressor (Costoya, ; Perez‐Torrado et al, ) that regulates Sp1‐dependent expression of the gastrin gene (Tillotson, ). ZFP608 represses Zfp609 , in turn repressing Rag1 and Rag2 , which are required for T‐cell receptor assembly and thymocyte development (Reed, Henderson, Oltz, & Aune, ; F. Zhang, Thomas, Oltz, & Aune, ). Future studies may focus on examining the dynamic expression of these genes in the head primordium as well as functional analysis to determine if their interaction with LHX1 plays a role in controlling the formation of the embryonic head.…”

Section: Discussionmentioning

confidence: 99%

“…ZFP608 represses Zfp609, in turn repressing Rag1 and Rag2, which are required for T-cell receptor assembly and thymocyte development (Reed, Henderson, Oltz, & Aune, 2013;F. Zhang, Thomas, Oltz, & Aune, 2006).…”

Section: Flag-lhx1 Hesx1mentioning

confidence: 99%

A gene regulatory network anchored by LIM homeobox 1 for embryonic head development

Sibbritt

Khoo

et al. 2018

Genesis

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Development of the embryonic head is driven by the activity of gene regulatory networks of transcription factors. LHX1 is a homeobox transcription factor that plays an essential role in the formation of the embryonic head. The loss of LHX1 function results in anterior truncation of the embryo caused by the disruption of morphogenetic movement of tissue precursors and the dysregulation of WNT signaling activity. Profiling the gene expression pattern in the Lhx1 mutant embryo revealed that tissues in anterior germ layers acquire posterior tissue characteristics, suggesting LHX1 activity is required for the allocation and patterning of head precursor tissues. Here, we used LHX1 as an entry point to delineate its transcriptional targets and interactors and construct a LHX1-anchored gene regulatory network. Using a gain-of-function approach, we identified genes that immediately respond to Lhx1 activation. Meta-analysis of the datasets of LHX1-responsive genes and genes expressed in the anterior tissues of mouse embryos at head-fold stage, in conjunction with published Xenopus embryonic LHX1 (Xlim1) ChIP-seq data, has pinpointed the putative transcriptional targets of LHX1 and an array of genetic determinants functioning together in the formation of the mouse embryonic head.

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“…However, cDKO T Conv cells had increased expression of Zfp618 (Supplementary Table 4) and T Regs had higher levels of Zfp608 (Supplementary Table 5). While little information exists as to the function of Zfp618 , Zfp608 has been described as a regulator of thymocyte development and a repressor of Rag gene expression[69, 70]. Unlike peripheral CD8α + and T Conv cells that have low Zfp608 expression upon thymic egress, T Regs maintain a relatively high level of the gene transcript (Immunological Genome Project database).…”

Section: Discussionmentioning

confidence: 99%

Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs

et al. 2016

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T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8α+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology.

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Reciprocal regulation of Rag expression in thymocytes by the zinc-finger proteins, Zfp608 and Zfp609

Cited by 12 publications

References 25 publications

Nipbl Interacts with Zfp609 and the Integrator Complex to Regulate Cortical Neuron Migration

Nipbl Interacts with Zfp609 and the Integrator Complex to Regulate Cortical Neuron Migration

A gene regulatory network anchored by LIM homeobox 1 for embryonic head development

Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs

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