H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells

Hezroni, Hadas; Tzchori, Itai; Davidi, Anna; Mattout, Anna; Biran, Alva; Nissim-Rafinia, Malka; Westphal, Heiner; Meshorer, Eran

doi:10.4161/nucl.2.4.16767

Cited by 68 publications

(70 citation statements)

References 44 publications

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“…S5 A and B). H3K9ac is found at actively transcribed promoters and is increased during neuronal differentiation (45). Consistent with the repressive epigenetic signature in SOX2-deficient hipNPCs, we found that H3K9ac levels were higher within the regulatory regions of poised proneural/neurogenic genes in shCTRL-than in shSOX2-expressing hipNPCs following exposure to Wnt3a (SI Appendix, Fig.…”

Section: Loss Of Sox2 Causes Impaired Transcriptional Activation Of Psupporting

confidence: 69%

SOX2 primes the epigenetic landscape in neural precursors enabling proper gene activation during hippocampal neurogenesis

Amador-Arjona

Cimadamore

Huang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

147

120

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Newborn granule neurons generated from neural progenitor cells (NPCs) in the adult hippocampus play a key role in spatial learning and pattern separation. However, the molecular mechanisms that control activation of their neurogenic program remain poorly understood. Here, we report a novel function for the pluripotency factor sex-determining region Y (SRY)-related HMG box 2 (SOX2) in regulating the epigenetic landscape of poised genes activated at the onset of neuronal differentiation. We found that SOX2 binds to bivalently marked promoters of poised proneural genes [neurogenin 2 (Ngn2) and neurogenic differentiation 1 (NeuroD1)] and a subset of neurogenic genes [e.g., SRY-box 21 (Sox21), brain-derived neurotrophic factor (Bdnf), and growth arrest and DNA-damage-inducible, beta (Gadd45b)] where it functions to maintain the bivalent chromatin state by preventing excessive polycomb repressive complex 2 activity. Conditional ablation of SOX2 in adult hippocampal NPCs impaired the activation of proneural and neurogenic genes, resulting in increased neuroblast death and functionally aberrant newborn neurons. We propose that SOX2 sets a permissive epigenetic state in NPCs, thus enabling proper activation of the neuronal differentiation program under neurogenic cue.SOX2 | neurogenesis | epigenetics C ell fate and differentiation decisions of adult neural progenitor cells (NPCs) are controlled by intrinsic and extrinsic signals from the neurogenic niche (1-3). Recent genomewide analyses of epigenetic regulators in the brain have provided considerable insight into the mechanisms that regulate neural development, neurological disease, and aging (4, 5). The chromatin states of NPCs change dynamically during cell-fate determination and cell differentiation, and chromatin marks such as histone H3 trimethylated Lys 27 (H3K27me3), histone H3 trimethylated Lys 4 (H3K4me3), and histone H3 acetylated Lys 9 (H3K9ac) are essential for regulating the expression of key genes involved in these processes (6). Sex-determining region Y (SRY)-related HMG box 2 (SOX2) is a member of the SOXB1 family of transcription factors, which play important roles in maintaining neural stem/progenitor cell properties, including their capacity to proliferate and self-renew (7,8). In humans, SOX2 mutations are associated with anophthalmia, defective hippocampal development, and seizures (9-11). Most patients with this syndrome experience intellectual disabilities (11), suggesting that loss of SOX2 function affects areas of the brain involved in cognition (e.g., hippocampus). SOX2 deficiency also causes neurodegeneration and impaired neurogenesis in the adult mouse brain (12, 13). However, the molecular mechanisms underlying the function of SOX2 in adult neurogenesis and its role in the human SOX2 anophthalmia syndrome are largely unknown.The subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus is a germinal zone of active neurogenesis during adulthood (14). Indeed, approximately one-third of DG neurons lost during this period are replaced ...

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Section: Loss Of Sox2 Causes Impaired Transcriptional Activation Of Psupporting

confidence: 69%

SOX2 primes the epigenetic landscape in neural precursors enabling proper gene activation during hippocampal neurogenesis

Amador-Arjona

Cimadamore

Huang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

147

120

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“…In line with published data on H3K9ac ChIPseq, in e.g. embryonic stem cell (ESC) nuclei, 14 we find H3K9ac signals not only restricted to the transcription start site (TSS) of genes (Fig. 2B), which is typical for mixed source distribution marks.…”

Section: Improving the Solid Gc Bias With Modifications To The Emulsisupporting

confidence: 91%

Sequencing on the SOLiD 5500xl System – in-depth characterization of the GC bias

Roeh

Weber

Rex‐Haffner

et al. 2017

Nucleus

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“…Site-specific histone acetylation and methylation patterns constitute the "histone code," leading to transcriptional activation and silencing (8 -10). Histone H3 lysine 9 and/or lysine 14 (H3K9/K14) acetylation, which is an epigenetic hallmark of transcriptionally active chromatin (11)(12)(13), participates in regulating the pluripotency and reprogramming capacity of ESCs (14). In addition, the pluripotency of ESCs is characterized by a specific epigenetic profile, which is distinct from that of differentiated progeny (7).…”

Section: Embryonic Stem Cells (Escs)mentioning

confidence: 99%

Dual Roles of Histone H3 Lysine 9 Acetylation in Human Embryonic Stem Cell Pluripotency and Neural Differentiation

Qiao

Wang

Yang³

et al. 2015

Journal of Biological Chemistry

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Background: H3K9Ac is an epigenetic mark representing transcriptionally active chromatin. Results: Inhibition of HDAC activity promotes pluripotency maintenance at the initiation of hESC differentiation and inhibits neural differentiation during neural commitment stage. Conclusion: H3K9Ac plays dual roles in hESC pluripotency maintenance and neural differentiation through regulating different targets. Significance: This work provides insight into the epigenetic mechanisms underlying neural differentiation of hESCs associated with histone acetylation patterns.

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H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells

Cited by 68 publications

References 44 publications

SOX2 primes the epigenetic landscape in neural precursors enabling proper gene activation during hippocampal neurogenesis

SOX2 primes the epigenetic landscape in neural precursors enabling proper gene activation during hippocampal neurogenesis

Sequencing on the SOLiD 5500xl System – in-depth characterization of the GC bias

Dual Roles of Histone H3 Lysine 9 Acetylation in Human Embryonic Stem Cell Pluripotency and Neural Differentiation

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