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Article ; Online: Histone editing elucidates the functional roles of H3K27 methylation and acetylation in mammals.

Sankar, Aditya / Mohammad, Faizaan / Sundaramurthy, Arun Kumar / Wang, Hua / Lerdrup, Mads / Tatar, Tulin / Helin, Kristian

Nature genetics

2022 Volume 54, Issue 6, Page(s) 754–760

Abstract: Posttranslational modifications of histones (PTMs) are associated with specific chromatin and gene expression ... ...

Abstract	Posttranslational modifications of histones (PTMs) are associated with specific chromatin and gene expression states
MeSH term(s)	Acetylation ; Animals ; Chromatin/genetics ; Chromatin/metabolism ; Drosophila melanogaster/genetics ; Histones/genetics ; Histones/metabolism ; Mammals/genetics ; Methylation ; Mice ; Polycomb Repressive Complex 2/genetics ; Protein Processing, Post-Translational/genetics
Chemical Substances	Chromatin ; Histones ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
Language	English
Publishing date	2022-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-022-01091-2
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Towards AR-assisted visualisation and guidance for imaging of dental decay.

Zhou, Yaxuan / Yoo, Paul / Feng, Yingru / Sankar, Aditya / Sadr, Alireza / Seibel, Eric J

Healthcare technology letters

2019 Volume 6, Issue 6, Page(s) 243–248

Abstract: Untreated dental decay is the most prevalent dental problem in the world, affecting up to 2.4 billion people and leading to a significant economic and social burden. Early detection can greatly mitigate irreversible effects of dental decay, avoiding the ... ...

Abstract	Untreated dental decay is the most prevalent dental problem in the world, affecting up to 2.4 billion people and leading to a significant economic and social burden. Early detection can greatly mitigate irreversible effects of dental decay, avoiding the need for expensive restorative treatment that forever disrupts the enamel protective layer of teeth. However, two key challenges exist that make early decay management difficult: unreliable detection and lack of quantitative monitoring during treatment. New optically based imaging through the enamel provides the dentist a safe means to detect, locate, and monitor the healing process. This work explores the use of an augmented reality (AR) headset to improve the workflow of early decay therapy and monitoring. The proposed workflow includes two novel AR-enabled features: (i) in situ visualisation of pre-operative optically based dental images and (ii) augmented guidance for repetitive imaging during therapy monitoring. The workflow is designed to minimise distraction, mitigate hand-eye coordination problems, and help guide monitoring of early decay during therapy in both clinical and mobile environments. The results from quantitative evaluations as well as a formative qualitative user study uncover the potentials of the proposed system and indicate that AR can serve as a promising tool in tooth decay management.
Language	English
Publishing date	2019-11-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2782924-8
ISSN	2053-3713
ISSN	2053-3713
DOI	10.1049/htl.2019.0082
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Article ; Online: PR-DUB maintains the expression of critical genes through FOXK1/2- and ASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1 deubiquitination.

Kolovos, Petros / Nishimura, Koutarou / Sankar, Aditya / Sidoli, Simone / Cloos, Paul A / Helin, Kristian / Christensen, Jesper

Genome research

2020 Volume 30, Issue 8, Page(s) 1119–1130

Abstract: Polycomb group proteins are important for maintaining gene expression patterns and cell identity in metazoans. The mammalian Polycomb repressive deubiquitinase (PR-DUB) complexes catalyze removal of monoubiquitination on lysine 119 of histone H2A ( ... ...

Abstract	Polycomb group proteins are important for maintaining gene expression patterns and cell identity in metazoans. The mammalian Polycomb repressive deubiquitinase (PR-DUB) complexes catalyze removal of monoubiquitination on lysine 119 of histone H2A (H2AK119ub1) through a multiprotein core comprised of BAP1, HCFC1, FOXK1/2, and OGT in combination with either of ASXL1, 2, or 3. Mutations in PR-DUB components are frequent in cancer. However, mechanistic understanding of PR-DUB function in gene regulation is limited. Here, we show that BAP1 is dependent on the ASXL proteins and FOXK1/2 in facilitating gene activation across the genome. Although PR-DUB was previously shown to cooperate with PRC2, we observed minimal overlap and functional interaction between BAP1 and PRC2 in embryonic stem cells. Collectively, these results demonstrate that PR-DUB, by counteracting accumulation of H2AK119ub1, maintains chromatin in an optimal configuration ensuring expression of genes important for general functions such as cell metabolism and homeostasis.
MeSH term(s)	Animals ; Cell Proliferation/genetics ; Cells, Cultured ; Chromatin/genetics ; Chromatin/metabolism ; Deubiquitinating Enzymes/genetics ; Deubiquitinating Enzymes/metabolism ; Forkhead Transcription Factors/metabolism ; Gene Expression Regulation/genetics ; Gene Knockout Techniques ; Histones/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Mouse Embryonic Stem Cells ; Polycomb-Group Proteins/genetics ; Polycomb-Group Proteins/metabolism ; Repressor Proteins/metabolism ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	ASXL2 protein, mouse ; Asxl1 protein, mouse ; BAP1 protein, mouse ; Chromatin ; Forkhead Transcription Factors ; FoxK2 protein, mouse ; Foxk1 protein, mouse ; Histones ; Polycomb-Group Proteins ; Repressor Proteins ; Tumor Suppressor Proteins ; Deubiquitinating Enzymes (EC 3.4.19.12) ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2020-08-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.261016.120
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Zs.A 3729: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Book ; Online: StableDreamer

Guo, Pengsheng / Hao, Hans / Caccavale, Adam / Ren, Zhongzheng / Zhang, Edward / Shan, Qi / Sankar, Aditya / Schwing, Alexander G. / Colburn, Alex / Ma, Fangchang

Taming Noisy Score Distillation Sampling for Text-to-3D

2023

Abstract: In the realm of text-to-3D generation, utilizing 2D diffusion models through score distillation sampling (SDS) frequently leads to issues such as blurred appearances and multi-faced geometry, primarily due to the intrinsically noisy nature of the SDS ... ...

Abstract	In the realm of text-to-3D generation, utilizing 2D diffusion models through score distillation sampling (SDS) frequently leads to issues such as blurred appearances and multi-faced geometry, primarily due to the intrinsically noisy nature of the SDS loss. Our analysis identifies the core of these challenges as the interaction among noise levels in the 2D diffusion process, the architecture of the diffusion network, and the 3D model representation. To overcome these limitations, we present StableDreamer, a methodology incorporating three advances. First, inspired by InstructNeRF2NeRF, we formalize the equivalence of the SDS generative prior and a simple supervised L2 reconstruction loss. This finding provides a novel tool to debug SDS, which we use to show the impact of time-annealing noise levels on reducing multi-faced geometries. Second, our analysis shows that while image-space diffusion contributes to geometric precision, latent-space diffusion is crucial for vivid color rendition. Based on this observation, StableDreamer introduces a two-stage training strategy that effectively combines these aspects, resulting in high-fidelity 3D models. Third, we adopt an anisotropic 3D Gaussians representation, replacing Neural Radiance Fields (NeRFs), to enhance the overall quality, reduce memory usage during training, and accelerate rendering speeds, and better capture semi-transparent objects. StableDreamer reduces multi-face geometries, generates fine details, and converges stably.
Keywords	Computer Science - Computer Vision and Pattern Recognition ; Computer Science - Artificial Intelligence
Subject code	006
Publishing date	2023-12-01
Publishing country	us
Document type	Book ; Online
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Article ; Online: Maternal expression of the histone demethylase Kdm4a is crucial for pre-implantation development.

Sankar, Aditya / Kooistra, Susanne Marije / Gonzalez, Javier Martin / Ohlsson, Claes / Poutanen, Matti / Helin, Kristian

Development (Cambridge, England)

2017 Volume 144, Issue 18, Page(s) 3264–3277

Abstract: Regulation of chromatin composition through post-translational modifications of histones contributes to transcriptional regulation and is essential for many cellular processes, including differentiation and development. KDM4A (JMJD2A) is a lysine ... ...

Abstract	Regulation of chromatin composition through post-translational modifications of histones contributes to transcriptional regulation and is essential for many cellular processes, including differentiation and development. KDM4A (JMJD2A) is a lysine demethylase with specificity towards di- and tri-methylated lysine 9 and lysine 36 of histone H3 (H3K9me2/me3 and H3K36me2/me3). Here, we report that
MeSH term(s)	Animals ; Cytokines/metabolism ; Embryo Implantation/genetics ; Embryo, Mammalian/metabolism ; Female ; Gene Expression Regulation, Developmental ; Genitalia, Female/metabolism ; Histone Demethylases/metabolism ; Infertility, Female/genetics ; Infertility, Female/pathology ; Mice, Inbred C57BL ; Mice, Knockout ; Pregnancy ; Signal Transduction ; Uterus/metabolism ; Zygote/metabolism
Chemical Substances	Cytokines ; Histone Demethylases (EC 1.14.11.-) ; JMJD2A protein, mouse (EC 1.14.11.-)
Language	English
Publishing date	2017--15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.155473
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Zs.MG 91: Show issues

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Article ; Online: KDM4A regulates the maternal-to-zygotic transition by protecting broad H3K4me3 domains from H3K9me3 invasion in oocytes.

Sankar, Aditya / Lerdrup, Mads / Manaf, Adeel / Johansen, Jens Vilstrup / Gonzalez, Javier Martin / Borup, Rehannah / Blanshard, Robert / Klungland, Arne / Hansen, Klaus / Andersen, Claus Yding / Dahl, John Arne / Helin, Kristian / Hoffmann, Eva R

Nature cell biology

2020 Volume 22, Issue 4, Page(s) 380–388

Abstract: The importance of germline-inherited post-translational histone modifications on priming early mammalian development is just ... ...

Abstract	The importance of germline-inherited post-translational histone modifications on priming early mammalian development is just emerging
MeSH term(s)	Animals ; Embryo Implantation ; Embryo, Mammalian ; Female ; Fertilization/genetics ; Heterochromatin/chemistry ; Heterochromatin/metabolism ; Histone Demethylases/genetics ; Histone Demethylases/metabolism ; Histones/genetics ; Histones/metabolism ; Male ; Metaphase ; Methylation ; Mice ; Mice, Knockout ; Oocytes/cytology ; Oocytes/growth & development ; Oocytes/metabolism ; Promoter Regions, Genetic ; Protein Processing, Post-Translational ; Transcription, Genetic ; Zygote/cytology ; Zygote/growth & development ; Zygote/metabolism
Chemical Substances	Heterochromatin ; Histones ; histone H3 trimethyl Lys4 ; Histone Demethylases (EC 1.14.11.-) ; JMJD2A protein, mouse (EC 1.14.11.-)
Language	English
Publishing date	2020-03-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-020-0494-z
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Zs.A 5169: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 12: Show issues

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Book ; Online: Equivariant Neural Rendering

Dupont, Emilien / Bautista, Miguel Angel / Colburn, Alex / Sankar, Aditya / Guestrin, Carlos / Susskind, Josh / Shan, Qi

2020

Abstract: We propose a framework for learning neural scene representations directly from images, without 3D supervision. Our key insight is that 3D structure can be imposed by ensuring that the learned representation transforms like a real 3D scene. Specifically, ... ...

Abstract	We propose a framework for learning neural scene representations directly from images, without 3D supervision. Our key insight is that 3D structure can be imposed by ensuring that the learned representation transforms like a real 3D scene. Specifically, we introduce a loss which enforces equivariance of the scene representation with respect to 3D transformations. Our formulation allows us to infer and render scenes in real time while achieving comparable results to models requiring minutes for inference. In addition, we introduce two challenging new datasets for scene representation and neural rendering, including scenes with complex lighting and backgrounds. Through experiments, we show that our model achieves compelling results on these datasets as well as on standard ShapeNet benchmarks. Comment: ICML 2020 camera ready
Keywords	Computer Science - Computer Vision and Pattern Recognition ; Statistics - Machine Learning
Publishing date	2020-06-13
Publishing country	us
Document type	Book ; Online
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Article ; Online: The Lysine Demethylase KDM5B Regulates Islet Function and Glucose Homeostasis.

Backe, Marie Balslev / Jin, Chunyu / Andreone, Luz / Sankar, Aditya / Agger, Karl / Helin, Kristian / Madsen, Andreas Nygaard / Poulsen, Steen Seier / Bysani, Madhusudhan / Bacos, Karl / Ling, Charlotte / Perone, Marcelo Javier / Holst, Birgitte / Mandrup-Poulsen, Thomas

Journal of diabetes research

2019 Volume 2019, Page(s) 5451038

Abstract: Aims: Posttranslational modifications of histones and transcription factors regulate gene expression and are implicated in beta-cell failure and diabetes. We have recently shown that preserving H3K27 and H3K4 methylation using the lysine demethylase ... ...

Abstract	Aims: Posttranslational modifications of histones and transcription factors regulate gene expression and are implicated in beta-cell failure and diabetes. We have recently shown that preserving H3K27 and H3K4 methylation using the lysine demethylase inhibitor GSK-J4 reduces cytokine-induced destruction of beta-cells and improves beta-cell function. Here, we investigate the therapeutic potential of GSK-J4 to prevent diabetes development and examine the importance of H3K4 methylation for islet function. Materials and methods: We used two mouse models of diabetes to investigate the therapeutic potential of GSK-J4. To clarify the importance of H3K4 methylation, we characterized a mouse strain with knockout (KO) of the H3K4 demethylase KDM5B. Results: GSK-J4 administration failed to prevent the development of experimental diabetes induced by multiple low-dose streptozotocin or adoptive transfer of splenocytes from acutely diabetic NOD to NODscid mice. KDM5B-KO mice were growth retarded with altered body composition, had low IGF-1 levels, and exhibited reduced insulin secretion. Interestingly, despite secreting less insulin, KDM5B-KO mice were able to maintain normoglycemia following oral glucose tolerance test, likely via improved insulin sensitivity, as suggested by insulin tolerance testing and phosphorylation of proteins belonging to the insulin signaling pathway. When challenged with high-fat diet, KDM5B-deficient mice displayed similar weight gain and insulin sensitivity as wild-type mice. Conclusion: Our results show a novel role of KDM5B in metabolism, as KDM5B-KO mice display growth retardation and improved insulin sensitivity.
MeSH term(s)	Animals ; Carbohydrate Metabolism/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/physiology ; Diabetes Mellitus, Experimental/chemically induced ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Experimental/metabolism ; Glucose/metabolism ; Growth Disorders/genetics ; Growth Disorders/metabolism ; Homeostasis/genetics ; Insulin Resistance/genetics ; Insulin-Secreting Cells/metabolism ; Insulin-Secreting Cells/physiology ; Islets of Langerhans/metabolism ; Islets of Langerhans/physiology ; Jumonji Domain-Containing Histone Demethylases/genetics ; Jumonji Domain-Containing Histone Demethylases/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Streptozocin
Chemical Substances	DNA-Binding Proteins ; Streptozocin (5W494URQ81) ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-) ; Kdm5b protein, mouse (EC 1.14.11.-) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2019-07-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2711897-6
ISSN	2314-6753 ; 2314-6753
ISSN (online)	2314-6753
ISSN	2314-6753
DOI	10.1155/2019/5451038
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Article ; Online: SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance.

Cruickshank, V Adam / Sroczynska, Patrycja / Sankar, Aditya / Miyagi, Satoru / Rundsten, Carsten Friis / Johansen, Jens Vilstrup / Helin, Kristian

PloS one

2015 Volume 10, Issue 11, Page(s) e0142806

Abstract: Alterations in chromatin structure caused by deregulated epigenetic mechanisms collaborate with underlying genetic lesions to promote cancer. SMARCA4/BRG1, a core component of the SWI/SNF ATP-dependent chromatin-remodelling complex, has been implicated ... ...

Abstract	Alterations in chromatin structure caused by deregulated epigenetic mechanisms collaborate with underlying genetic lesions to promote cancer. SMARCA4/BRG1, a core component of the SWI/SNF ATP-dependent chromatin-remodelling complex, has been implicated by its mutational spectrum as exerting a tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the three proteins demonstrate that they are required for the expression of haematopoietic stem cell associated genes but in contrast to previous results obtained in mouse cells, the three proteins are not required for the expression of c-MYC regulated genes.
MeSH term(s)	Animals ; Cell Cycle ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Cell Self Renewal ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Helicases/metabolism ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation, Leukemic ; Gene Knockdown Techniques ; Gene Rearrangement ; Leukemia/genetics ; Leukemia/pathology ; Mice ; Muscle Proteins/metabolism ; Myeloid Cells/pathology ; Myeloid-Lymphoid Leukemia Protein/genetics ; Nuclear Proteins/metabolism ; Protein Subunits/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Repressor Proteins/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic
Chemical Substances	Chromosomal Proteins, Non-Histone ; DNA-Binding Proteins ; DPF2 protein, human ; DPF2 protein, mouse ; Muscle Proteins ; Nuclear Proteins ; Protein Subunits ; Proto-Oncogene Proteins c-myc ; Repressor Proteins ; SMARCD2 protein, human ; SWI-SNF-B chromatin-remodeling complex ; Smarcd2 protein, mouse ; Transcription Factors ; Myeloid-Lymphoid Leukemia Protein (149025-06-9) ; SMARCA4 protein, human (EC 3.6.1.-) ; Smarca4 protein, mouse (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0142806
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Article ; Online: ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells.

Riso, Vincenzo / Cammisa, Marco / Kukreja, Harpreet / Anvar, Zahra / Verde, Gaetano / Sparago, Angela / Acurzio, Basilia / Lad, Shraddha / Lonardo, Enza / Sankar, Aditya / Helin, Kristian / Feil, Robert / Fico, Annalisa / Angelini, Claudia / Grimaldi, Giovanna / Riccio, Andrea

Nucleic acids research

2016 Volume 44, Issue 17, Page(s) 8165–8178

Abstract: ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target ... ...

Abstract	ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS and non-ICRBS suggesting that different cis-acting regulatory functions are repressed by ZFP57 at these two classes of target loci. Overall, these data demonstrate that ZFP57 is pivotal to maintain the allele-specific epigenetic modifications of ICRs that in turn are necessary for maintaining the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet required.
MeSH term(s)	Animals ; Binding Sites/genetics ; Cell Differentiation/genetics ; CpG Islands/genetics ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Genetic Loci ; Genomic Imprinting ; Histones/metabolism ; Lysine/metabolism ; Methylation ; Mice ; Models, Genetic ; Mouse Embryonic Stem Cells/metabolism ; Nuclear Proteins/metabolism ; Repressor Proteins/metabolism
Chemical Substances	Histones ; Nuclear Proteins ; Repressor Proteins ; Zfp-57 protein, mouse ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2016-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkw505
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