Fam60a defines a variant Sin3a‐Hdac complex in embryonic stem cells required for self‐renewal

Streubel, Gundula; Fitzpatrick, Darren J.; Oliviero, Giorgio; Scelfo, Andrea; Moran, Bruce; Das, Sudipto; Munawar, Nayla; Watson, Ariane; Wynne, Kieran; Negri, Gian Luca; Dillon, Eugene; Jammula, Sri Ganesh; Hokamp, Karsten; O’Connor, Darran P.; Pasini, Diego; Cagney, Gerard; Bracken, Adrian P.

doi:10.15252/embj.201696307

Cited by 47 publications

(72 citation statements)

References 89 publications

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“…To determine the set of genes affected by both Pali1 and Aebp2, we took the top three thousand H3K27me3 positive genes and computed the intersection of those genes that lose H3K27me3 in the Pali1/2 double knockout and gain H3K27me3 in the Aebp2 gene trap. Data for H3K27me3 was taken from GSE81081 and processed as previously described (Streubel et al, 2017). In brief, reads were aligned to the mouse reference genome (mm10) using Bowtie2 v2.1.0 (Langmead and Salzberg, 2012) and peaks determined using macs2 v2.1.1 (Feng et al, 2012).…”

Section: Continuedmentioning

confidence: 99%

A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities

et al. 2018

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The polycomb repressive complex 2 (PRC2) consists of core subunits SUZ12, EED, RBBP4/7, and EZH1/2 and is responsible for mono-, di-, and tri-methylation of lysine 27 on histone H3. Whereas two distinct forms exist, PRC2.1 (containing one polycomb-like protein) and PRC2.2 (containing AEBP2 and JARID2), little is known about their differential functions. Here, we report the discovery of a family of vertebrate-specific PRC2.1 proteins, "PRC2 associated LCOR isoform 1" (PALI1) and PALI2, encoded by the LCOR and LCORL gene loci, respectively. PALI1 promotes PRC2 methyltransferase activity in vitro and in vivo and is essential for mouse development. Pali1 and Aebp2 define mutually exclusive, antagonistic PRC2 subtypes that exhibit divergent H3K27-tri-methylation activities. The balance of these PRC2.1/PRC2.2 activities is required for the appropriate regulation of polycomb target genes during differentiation. PALI1/2 potentially link polycombs with transcriptional co-repressors in the regulation of cellular identity during development and in cancer.

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Section: Continuedmentioning

confidence: 99%

A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities

et al. 2018

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“…Using a proteomics approach, a recent study identified SIN3-HDAC Complex Associated Factor (FAM60A, also known as SINHCAF) as a new ESC-specific subunit of the Sin3a-HDAC complex (Streubel et al, 2017). FAM60A colocalizes genome-wide with other complex members at promoters and is required for SIN3A localization.…”

Section: Histone Deacetylasesmentioning

confidence: 99%

Epigenetic control of transcriptional regulation in pluripotency and early differentiation

Gökbuget

Blelloch

2019

Development

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Pluripotent stem cells give rise to all cells of the adult organism, making them an invaluable tool in regenerative medicine. In response to differentiation cues, they can activate markedly distinct lineagespecific gene networks while turning off or rewiring pluripotency networks. Recent innovations in chromatin and nuclear structure analyses combined with classical genetics have led to novel insights into the transcriptional and epigenetic mechanisms underlying these networks. Here, we review these findings in relation to their impact on the maintenance of and exit from pluripotency and highlight the many factors that drive these processes, including histone modifying enzymes, DNA methylation and demethylation, nucleosome remodeling complexes and transcription factor-mediated enhancer switching.

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“…3). O-GlcNAcylation is thought to be involved in key cellular processes such as gene regulation and expression [22][23][24], metabolic activity [25], and cellcycle regulation [26]. Changes in O-GlcNAc homoeostasis have been linked to severe developmental problems and neurodegenerative diseases [27][28][29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

An intellectual disability syndrome with single-nucleotide variants in O-GlcNAc transferase

et al. 2020

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Intellectual disability (ID) is a neurodevelopmental condition that affects~1% of the world population. In total 5−10% of ID cases are due to variants in genes located on the X chromosome. Recently, variants in OGT have been shown to co-segregate with X-linked intellectual disability (XLID) in multiple families. OGT encodes O-GlcNAc transferase (OGT), an essential enzyme that catalyses O-linked glycosylation with β-N-acetylglucosamine (O-GlcNAc) on serine/threonine residues of thousands of nuclear and cytosolic proteins. In this review, we compile the work from the last few years that clearly delineates a new syndromic form of ID, which we propose to classify as a novel Congenital Disorder of Glycosylation (OGT-CDG). We discuss potential hypotheses for the underpinning molecular mechanism(s) that provide impetus for future research studies geared towards informed interventions.

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Fam60a defines a variant Sin3a‐Hdac complex in embryonic stem cells required for self‐renewal

Cited by 47 publications

References 89 publications

A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities

A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities

Epigenetic control of transcriptional regulation in pluripotency and early differentiation

An intellectual disability syndrome with single-nucleotide variants in O-GlcNAc transferase

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