Replication-dependent histone genes are actively transcribed in differentiating and aging retinal neurons

Banday, Abdul Rouf; Baumgartner, Marybeth; Seesi, Sahar Al; Karunakaran, Devi Krishna Priya; Venkatesh, Aditya; Congdon, Sean; Lemoine, Christopher; Kilcollins, Ashley M; Măndoiu, Ion; Punzo, Claudio; Kanadia, Rahul N.

doi:10.4161/15384101.2015.941757

Cited by 20 publications

(29 citation statements)

References 51 publications

(78 reference statements)

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“…The upregulation of both Hist1h1a and HistIh1c may reflect the role of histone H1 in chromatin condensation and the reprogramming of heterochromatic regions we observed. This agrees with recent studies that have shown differential expression of histone variants from within HIST1 and HIST2 during development and in senescent mouse neurons [74]. Higher resolution analyses of the chromatin structural changes that occur within patch three of the HIST1 cluster, using either paused and elongating Pol II-specific ChiA-Pet [75] or circular chromosome conformation capture [76], would help to understand the regulatory cascade that is controlling histone variant expression in differentiated myotubes.…”

Section: Discussionsupporting

confidence: 88%

Linkages between changes in the 3D organization of the genome and transcription during myotube differentiation in vitro

et al. 2017

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BackgroundThe spatial organization of eukaryotic genomes facilitates and reflects the underlying nuclear processes that are occurring in the cell. As such, the spatial organization of a genome represents a window on the genome biology that enables analysis of the nuclear regulatory processes that contribute to mammalian development.MethodsIn this study, Hi-C and RNA-seq were used to capture the genome organization and transcriptome in mouse muscle progenitor cells (C2C12 myoblasts) before and after differentiation to myotubes, in the presence or absence of the cytidine analogue AraC.ResultsWe observed significant local and global developmental changes despite high levels of correlation between the myotubes and myoblast genomes. Notably, the genes that exhibited the greatest variation in transcript levels between the different developmental stages were predominately within the euchromatic compartment. There was significant re-structuring and changes in the expression of replication-dependent histone variants within the HIST1 locus. Finally, treating terminally differentiated myotubes with AraC resulted in additional changes to the transcriptome and 3D genome organization of sets of genes that were all involved in pyroptosis.ConclusionsCollectively, our results provide evidence for muscle cell-specific responses to developmental and environmental stimuli mediated through a chromatin structure mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-017-0122-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 88%

Linkages between changes in the 3D organization of the genome and transcription during myotube differentiation in vitro

et al. 2017

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“…Quite unexpectedly, all gene clusters displaying dynamic diurnal binding of the two MeCP2 isoforms were also enriched in genes encoding replication-dependent (RD) histones. Expression of RD histones has been recently detected in terminally differentiated cells and tissues, including neurons and brain (65, 66). Some of these genes encode histone isotypes with a certain sequence divergence (65), and could possibly affect the histone interactions within the nucleosome.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of RD histones has been recently detected in terminally differentiated cells and tissues, including neurons and brain (65, 66). Some of these genes encode histone isotypes with a certain sequence divergence (65), and could possibly affect the histone interactions within the nucleosome. Further analyses will be required to assess if MeCP2 has any regulatory effect on the expression of such genes, but it is tempting to speculate a possible role in the generation of variant nucleosomes present in adult brain (65).…”

Section: Discussionmentioning

confidence: 99%

MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2

Paz

Khajavi

Martin

et al. 2018

Preprint

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MeCP2 -a chromatin-binding protein associated with Rett syndrome -has two main isoforms, MeCP2-E1 and MeCP2-E2, with 96% amino acid identity differing in a few N-terminal amino acid residues. Previous studies have shown brain region-specific expression of these isoforms which, in addition to their different cellular localization and differential expression during brain development, suggest they may also have nonoverlapping molecular mechanisms. However, differential functions of MeCP2-E1 and E2 remain largely unexplored. Here, we show that the N-terminal domains (NTD) of MeCP2-E1 and E2 modulate the ability of the methyl binding domain (MBD) to interact with DNA as well as influencing the turnover rates, binding dynamics, response to nuclear depolarization, and circadian oscillations of the two isoforms. Our proteomics data indicate that both isoforms exhibit unique interacting protein partners. Moreover, genome-wide analysis using ChIP-seq provide evidence for a shared as well as a specific regulation of different sets of genes. Our findings provide insight into the functional complexity of MeCP2 by dissecting differential aspects of its two isoforms.All rights reserved. No reuse allowed without permission.

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“…CD1 mouse retinae were collected at embryonic day (E) 16 and postnatal day (P) 0. RNA was isolated using the Thermo Scientific NE‐PER Nuclear and Cytoplasmic Extraction Kit (Thermo Fisher Scientific), as described previously (Banday et al, ). The cytoplasmic samples were then used for RNAseq on the Illumina HighSeq 2000 platform.…”

Section: Methodsmentioning

confidence: 99%

“…Retinae from CD1 mice at different stages of development (E12, E14, E16, E18, P0, P4, and P25) were harvested and subjected to the RNA fractionation as previously described (Banday et al, ). One µg of the cytoplasmic RNA was then used for microarray analysis, which was performed at the Yale Center for Genome Analysis.…”

Section: Methodsmentioning

confidence: 99%

Minor splicing snRNAs are enriched in the developing mouse CNS and are crucial for survival of differentiating retinal neurons

Baumgartner

Lemoine

Seesi

et al. 2014

Developmental Neurobiology

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In eukaryotes, gene expression requires splicing, which starts with the identification of exon-intron boundaries by the small, nuclear RNA (snRNAs) of the spliceosome, aided by associated proteins. In the mammalian genome, <1% of introns lack canonical exon-intron boundary sequences and cannot be spliced by the canonical splicing machinery. These introns are spliced by the minor spliceosome, consisting of unique snRNAs (U11, U12, U4atac, and U6atac). The importance of the minor spliceosome is underscored by the disease microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1), which is caused by mutation in U4atac. Thus, it is important to understand the expression and function of the minor spliceosome and its targets in mammalian development, for which we used the mouse as our model. Here, we report enrichment of the minor snRNAs in the developing head/central nervous system (CNS) between E9.5 and E12.5, along with enrichment of these snRNAs in differentiating retinal neurons. Moreover, dynamic expression kinetics of minor intron-containing genes (MIGs) was observed across retinal development. DAVID analysis of MIGs that were cotranscriptionally upregulated embryonically revealed enrichment for RNA metabolism and cell cycle regulation. In contrast, MIGs that were cotranscriptionally upregulated postnatally revealed enrichment for protein localization/transport, vesicle-mediated transport, and calcium transport. Finally, we used U12 morpholino to inactivate the minor spliceosome in the postnatal retina, which resulted in apoptosis of differentiating retinal neurons. Taken together, our data suggest that the minor spliceosome may have distinct functions in embryonic versus postnatal development. Importantly, we show that the minor spliceosome is crucial for the survival of terminally differentiating retinal neurons.

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Replication-dependent histone genes are actively transcribed in differentiating and aging retinal neurons

Cited by 20 publications

References 51 publications

Linkages between changes in the 3D organization of the genome and transcription during myotube differentiation in vitro

Linkages between changes in the 3D organization of the genome and transcription during myotube differentiation in vitro

MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2

Minor splicing snRNAs are enriched in the developing mouse CNS and are crucial for survival of differentiating retinal neurons

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