Chromatin Dynamics and Higher-Order Chromatin Organization

Zeilner, Anette; Piatti, Paolo; Lusser, Alexandra

doi:10.1002/3527600906.mcb.201100027

Cited by 2 publications

(2 citation statements)

References 168 publications

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“…Eukaryotic chromatin, which consists of nuclear DNA complexed with the conserved histone proteins H2A, H2B, H3, H4 and H1 as well as many additional architectural proteins, is a highly dynamic structure that changes in response to external and internal cues as well as during developmental and differentiation-related processes. DNA methylation, histone modification and the incorporation of histone variants strongly affect the functional and structural properties of chromatin (Maison and Almouzni, 2004; Piatti et al, 2011; Zeilner et al, 2012). In addition, the activity of ATP-dependent chromatin remodeling factors (ChRFs) that modulate the interaction between histones and DNA causes the loss or gain of nucleosomes, altered rotational and translational positioning of a nucleosome, histone exchange or changes in nucleosomal structure (Lusser and Kadonaga, 2003; Clapier and Cairns, 2009).…”

Section: Introductionmentioning

confidence: 99%

Role for Chromatin Remodeling Factor Chd1 in Learning and Memory

Schoberleitner

Mutti

Sah

et al. 2019

Front. Mol. Neurosci.

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Precise temporal and spatial regulation of gene expression in the brain is a prerequisite for cognitive processes such as learning and memory. Epigenetic mechanisms that modulate the chromatin structure have emerged as important regulators in this context. While posttranslational modification of histones or the modification of DNA bases have been examined in detail in many studies, the role of ATP-dependent chromatin remodeling factors (ChRFs) in learning- and memory-associated gene regulation has largely remained obscure. Here we present data that implicate the highly conserved chromatin assembly and remodeling factor Chd1 in memory formation and the control of immediate early gene (IEG) response in the hippocampus. We used various paradigms to assess short-and long-term memory in mice bearing a mutated Chd1 gene that gives rise to an N-terminally truncated protein. Our data demonstrate that the Chd1 mutation negatively affects long-term object recognition and short- and long-term spatial memory. We found that Chd1 regulates hippocampal expression of the IEG early growth response 1 (Egr1) and activity-regulated cytoskeleton-associated (Arc) but not cFos and brain derived neurotrophic factor (Bdnf), because the Chd1-mutation led to dysregulation of Egr1 and Arc expression in naive mice and in mice analyzed at different stages of object location memory (OLM) testing. Of note, Chd1 likely regulates Egr1 in a direct manner, because chromatin immunoprecipitation (ChIP) assays revealed enrichment of Chd1 upon stimulation at the Egr1 genomic locus in the hippocampus and in cultured cells. Together these data support a role for Chd1 as a critical regulator of molecular mechanisms governing memory-related processes, and they show that this function involves the N-terminal serine-rich region of the protein.

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Section: Introductionmentioning

confidence: 99%

Role for Chromatin Remodeling Factor Chd1 in Learning and Memory

Schoberleitner

Mutti

Sah

et al. 2019

Front. Mol. Neurosci.

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“…The organization of chromatin in the nucleus is not uniform but consists of areas with distinct features often reflecting the functional state of the region. The highly condensed heterochromatin comprises areas with low transcription activity while the more “open” euchromatin is highly permissible for transcription 2 . The relative proportions of these chromatin states can vary greatly in different cell types.…”

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Embryonic stem cell differentiation requires full length Chd1

Piatti

Lim

Nat

et al. 2015

Sci Rep

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The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the effects of a partial deletion of the gene encoding the chromatin remodeling factor Chd1 that generates an N-terminally truncated version of Chd1 in mouse ESCs in vitro as well as in vivo. We found that a previously uncharacterized serine-rich region (SRR) at the N-terminus is not required for chromatin assembly activity of Chd1 but that it is subject to phosphorylation. Expression of Chd1 lacking this region in ESCs resulted in aberrant differentiation properties of these cells. The self-renewal capacity and ESC chromatin structure, however, were not affected. Notably, we found that newly established ESCs derived from Chd1Δ2/Δ2 mutant mice exhibited similar differentiation defects as in vitro generated mutant ESCs, even though the N-terminal truncation of Chd1 was fully compatible with embryogenesis and post-natal life in the mouse. These results underscore the importance of Chd1 for the regulation of pluripotency in ESCs and provide evidence for a hitherto unrecognized critical role of the phosphorylated N-terminal SRR for full functionality of Chd1.

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Chromatin Dynamics and Higher-Order Chromatin Organization

Cited by 2 publications

References 168 publications

Role for Chromatin Remodeling Factor Chd1 in Learning and Memory

Role for Chromatin Remodeling Factor Chd1 in Learning and Memory

Embryonic stem cell differentiation requires full length Chd1

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