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Article ; Online: Enhancers of the PAIR4 regulatory module promote distal V

Hill, Louisa / Jaritz, Markus / Tagoh, Hiromi / Schindler, Karina / Kostanova-Poliakova, Daniela / Sun, Qiong / Schwickert, Tanja A / Leeb, Martin / Busslinger, Meinrad

The EMBO journal

2023 Volume 42, Issue 15, Page(s) e112741

Abstract: While extended loop extrusion across the entire Igh locus controls ... ...

Abstract	While extended loop extrusion across the entire Igh locus controls V
MeSH term(s)	Regulatory Sequences, Nucleic Acid/genetics ; Precursor Cells, B-Lymphoid ; Binding Sites ; Recombination, Genetic
Language	English
Publishing date	2023-06-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.15252/embj.2022112741
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Article ; Online: Enhancer-promoter interactions are reconfigured through the formation of long-range multiway hubs as mouse ES cells exit pluripotency.

Lando, David / Ma, Xiaoyan / Cao, Yang / Jartseva, Aleksandra / Stevens, Tim J / Boucher, Wayne / Reynolds, Nicola / Montibus, Bertille / Hall, Dominic / Lackner, Andreas / Ragheb, Ramy / Leeb, Martin / Hendrich, Brian D / Laue, Ernest D

Molecular cell

2024 Volume 84, Issue 8, Page(s) 1406–1421.e8

Abstract: Enhancers bind transcription factors, chromatin regulators, and non-coding transcripts to modulate the expression of target genes. Here, we report 3D genome structures of single mouse ES cells as they are induced to exit pluripotency and transition ... ...

Abstract	Enhancers bind transcription factors, chromatin regulators, and non-coding transcripts to modulate the expression of target genes. Here, we report 3D genome structures of single mouse ES cells as they are induced to exit pluripotency and transition through a formative stage prior to undergoing neuroectodermal differentiation. We find that there is a remarkable reorganization of 3D genome structure where inter-chromosomal intermingling increases dramatically in the formative state. This intermingling is associated with the formation of a large number of multiway hubs that bring together enhancers and promoters with similar chromatin states from typically 5-8 distant chromosomal sites that are often separated by many Mb from each other. In the formative state, genes important for pluripotency exit establish contacts with emerging enhancers within these multiway hubs, suggesting that the structural changes we have observed may play an important role in modulating transcription and establishing new cell identities.
MeSH term(s)	Mice ; Animals ; Mouse Embryonic Stem Cells/metabolism ; Regulatory Sequences, Nucleic Acid ; Embryonic Stem Cells/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Chromatin/genetics ; Chromatin/metabolism ; Enhancer Elements, Genetic
Chemical Substances	Transcription Factors ; Chromatin
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2024.02.015
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Article ; Online: Using fecal immmunochemical cartridges for gut microbiome analysis within a colorectal cancer screening program.

Brezina, Stefanie / Borkovec, Martin / Baierl, Andreas / Bastian, Fabienne / Futschik, Andreas / Gasche, Nikolaus / Gruenberger, Thomas / Hallas, Michael / Jannsen, Christian / Leeb, Gernot / Lutz, Rebecca / Sladek, Barbara / Gsur, Andrea

Gut microbes

2023 Volume 15, Issue 1, Page(s) 2176119

Abstract: The colorectal cancer (CRC) screening program B-PREDICT is an invited two-stage screening project using a fecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. Since the gut microbiome likely plays ...

Abstract	The colorectal cancer (CRC) screening program B-PREDICT is an invited two-stage screening project using a fecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. Since the gut microbiome likely plays a role in the etiology of CRC, microbiome-based biomarkers in combination with FIT could be a promising tool for optimizing CRC screening. Therefore, we evaluated the usability of FIT cartridges for microbiome analysis and compared it to Stool Collection and Preservation Tubes. Corresponding FIT cartridges as well as Stool Collection and Preservation Tubes were collected from participants of the B-PREDICT screening program to perform 16S rRNA gene sequencing. We calculated intraclass correlation coefficients (ICCs) based on center log ratio transformed abundances and used ALDEx2 to test for significantly differential abundant taxa between the two sample types. Additionally, FIT and Stool Collection and Preservation Tube triplicate samples were obtained from volunteers to estimate variance components of microbial abundances. FIT and Preservation Tube samples produce highly similar microbiome profiles which cluster according to subject. Significant differences between the two sample types can be found for abundances of some bacterial taxa (e.g. 33 genera) but are minor compared to the differences between the subjects. Analysis of triplicate samples revealed slightly worse repeatability of results for FIT than for Preservation Tube samples. Our findings indicate that FIT cartridges are appropriate for gut microbiome analysis nested within CRC screening programs.
MeSH term(s)	Humans ; Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Early Detection of Cancer/methods ; Microbiota ; Colorectal Neoplasms/diagnosis ; Feces/microbiology
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2575755-6
ISSN	1949-0984 ; 1949-0984
ISSN (online)	1949-0984
ISSN	1949-0984
DOI	10.1080/19490976.2023.2176119
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Article ; Online: Antibiotics: a shot in the arm.

Leeb, Martin

Nature

2004 Volume 431, Issue 7011, Page(s) 892–893

MeSH term(s)	Animals ; Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/economics ; Anti-Bacterial Agents/pharmacology ; Drug Design ; Drug Evaluation, Preclinical/economics ; Drug Industry/economics ; Drug Industry/trends ; Drug Resistance, Bacterial ; Humans ; Patents as Topic ; United States ; United States Food and Drug Administration
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2004-10-21
Publishing country	England
Document type	News
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/431892a
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Article ; Online: Gasping for victory.

Leeb, Martin

Nature

2004 Volume 430, Issue 7000, Page(s) 608–609

MeSH term(s)	Acclimatization/physiology ; Air Pollution/adverse effects ; Asthma/etiology ; Asthma/physiopathology ; Asthma/prevention & control ; Atmosphere/chemistry ; Carbon/adverse effects ; Carbon/analysis ; Greece ; Heat Stroke/etiology ; Heat Stroke/physiopathology ; Heat Stroke/prevention & control ; Hot Temperature ; Humans ; Ozone/adverse effects ; Ozone/analysis ; Physical Endurance/physiology ; Physical Exertion/physiology ; Running/physiology ; Sports/physiology
Chemical Substances	Ozone (66H7ZZK23N) ; Carbon (7440-44-0)
Language	English
Publishing date	2004-08-05
Publishing country	England
Document type	News
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/430608a
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Article: Haploid genomes illustrate epigenetic constraints and gene dosage effects in mammals.

Leeb, Martin / Wutz, Anton

Epigenetics & chromatin

2013 Volume 6, Issue 1, Page(s) 41

Abstract: Sequencing projects have revealed the information of many animal genomes and thereby enabled the exploration of genome evolution. Insights into how genomes have been repeatedly modified provide a basis for understanding evolutionary innovation and the ... ...

Abstract	Sequencing projects have revealed the information of many animal genomes and thereby enabled the exploration of genome evolution. Insights into how genomes have been repeatedly modified provide a basis for understanding evolutionary innovation and the ever increasing complexity of animal developmental programs. Animal genomes are diploid in most cases, suggesting that redundant information in two copies of the genome increases evolutionary fitness. Genomes are well adapted to a diploid state. Changes of ploidy can be accommodated early in development but they rarely permit successful development into adulthood. In mammals, epigenetic mechanisms including imprinting and X inactivation restrict haploid development. These restrictions are relaxed in an early phase of development suggesting that dosage regulation appears less critical. Here we review the recent literature on haploid genomes and dosage effects and try to embed recent findings in an evolutionary perspective.
Language	English
Publishing date	2013-12-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2462129-8
ISSN	1756-8935
ISSN	1756-8935
DOI	10.1186/1756-8935-6-41
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Article ; Online: Breast cancer hypoxia in relation to prognosis and benefit from radiotherapy after breast-conserving surgery in a large, randomised trial with long-term follow-up.

Tutzauer, Julia / Sjöström, Martin / Holmberg, Erik / Karlsson, Per / Killander, Fredrika / Leeb-Lundberg, L M Fredrik / Malmström, Per / Niméus, Emma / Fernö, Mårten / Jögi, Annika

British journal of cancer

2022 Volume 126, Issue 8, Page(s) 1145–1156

Abstract: Background: Breast-conserving surgery followed by radiotherapy is part of standard treatment for early-stage breast cancer. Hypoxia is common in cancer and may affect the benefit of radiotherapy. Cells adapt to hypoxic stress largely via the ... ...

Abstract	Background: Breast-conserving surgery followed by radiotherapy is part of standard treatment for early-stage breast cancer. Hypoxia is common in cancer and may affect the benefit of radiotherapy. Cells adapt to hypoxic stress largely via the transcriptional activity of hypoxia-inducible factor (HIF)-1α. Here, we aim to determine whether tumour HIF-1α-positivity and hypoxic gene-expression signatures associated with the benefit of radiotherapy, and outcome. Methods: Tumour HIF-1α-status and expression of hypoxic gene signatures were retrospectively analysed in a clinical trial where 1178 women with primary T1-2N0M0 breast cancer were randomised to receive postoperative radiotherapy or not and followed 15 years for recurrence and 20 years for breast cancer death. Results: The benefit from radiotherapy was similar in patients with HIF-1α-positive and -negative primary tumours. Both ipsilateral and any breast cancer recurrence were more frequent in women with HIF-1α-positive primary tumours (hazard ratio, HR Conclusions: The benefit of postoperative radiotherapy persisted in patients with hypoxic primary tumours. Patients with hypoxic primary breast tumours had an increased risk of recurrence and breast cancer death.
MeSH term(s)	Breast Neoplasms/genetics ; Breast Neoplasms/radiotherapy ; Breast Neoplasms/surgery ; Female ; Follow-Up Studies ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Mastectomy, Segmental ; Neoplasm Recurrence, Local/radiotherapy ; Prognosis ; Retrospective Studies
Chemical Substances	Hypoxia-Inducible Factor 1, alpha Subunit
Language	English
Publishing date	2022-02-09
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-021-01630-4
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Article: Associations Between Parental Occupational Balance, Subjective Health, and Clinical Characteristics of VLBW Infants.

Dür, Mona / Röschel, Anna / Oberleitner-Leeb, Christiane / Herrmanns, Verena / Pichler-Stachl, Elisabeth / Mattner, Barbara / Pernter, Silvia-Desiree / Wald, Martin / Urlesberger, Berndt / Kurz, Herbert / Frischer, Thomas / Zwiauer, Karl / Matter, Inu Sarah / Berger, Angelika

Frontiers in pediatrics

2022 Volume 10, Page(s) 816221

Abstract: Objective: Very low birthweight (VLBW) infants have an increased risk of mortality and frequently suffer from complications, which affects parental occupational balance. Occupational balance is the satisfaction with one's meaningful activities, which ... ...

Abstract	Objective: Very low birthweight (VLBW) infants have an increased risk of mortality and frequently suffer from complications, which affects parental occupational balance. Occupational balance is the satisfaction with one's meaningful activities, which include everyday activities that people need to, want to, and are expected to do. In contrast to work-life balance, the construct of occupational balance addresses different activities equally and it applies to all persons, regardless of whether they are working or not. Parental occupational balance might be related to parents' and VLBW infants' health. Therefore, the objective of this study was to investigate associations between parental occupational balance, subjective health, and clinical characteristics of VLBW infants. Methods: A cross-sectional multicenter study was conducted in six Austrian neonatal intensive care units. Occupational balance and subjective health of parents of VLBW infants were assessed with six self-reported questionnaires. The following clinical characteristics of VLBW infants were extracted from medical records: gestational age, birthweight, Apgar scores, Clinical Risk for Babies II Score, and complications of prematurity. Spearman's rank coefficients were calculated. Results: In total, 270 parents, 168 (62%) female and their VLBW infants, 120 (44%) female, were included in this study. Parents' mean age was 33.7 (±6.0) years, mean gestational age of VLBW infants was 27 + 3 (±2) weeks. Associations between parental occupational balance, subjective health, and clinical characteristics of VLBW infants were identified ( Conclusion: Occupational balance is associated with parents' and VLBW infants' health. Interventions to strengthen parental occupational balance might increase parental health and thereby also improve health and developmental outcomes of their VLBW infants.
Language	English
Publishing date	2022-03-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2022.816221
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Article ; Online: Establishment of epigenetic patterns in development.

Leeb, Martin / Wutz, Anton

Chromosoma

2012 Volume 121, Issue 3, Page(s) 251–262

Abstract: The distinct cell types of the body are established from the fertilized egg in development and assembled into functional tissues. Functional characteristics and gene expression patterns are then faithfully maintained in somatic cell lineages over a ... ...

Abstract	The distinct cell types of the body are established from the fertilized egg in development and assembled into functional tissues. Functional characteristics and gene expression patterns are then faithfully maintained in somatic cell lineages over a lifetime. On the molecular level, transcription factors initiate lineage-specific gene expression programmmes and epigenetic regulation contributes to stabilization of expression patterns. Epigenetic mechanisms are essential for maintaining stable cell identities and their disruption can lead to disease or cellular transformation. Here, we discuss the role of epigenetic regulation in the early mouse embryo, which presents a relatively well-understood system. A number of studies have contributed to the understanding of the function of Polycomb group complexes and the DNA methylation system. The role of many other chromatin regulators in development remains largely unexplored. Albeit the current picture remains incomplete, the view emerges that multiple epigenetic mechanisms cooperate for repressing critical developmental regulators. Some chromatin modifications appear to act in parallel and others might repress the same gene at a different stage of cell differentiation. Studies in pluripotent mouse embryonic stem cells show that epigenetic mechanisms function to repress lineage specific gene expression and prevent extraembryonic differentiation. Insights into this epigenetic "memory" of the first lineage decisions help to provide a better understanding of the function of epigenetic regulation in adult stem cell differentiation.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Lineage/genetics ; DNA Methylation ; Embryonic Stem Cells/cytology ; Endosomal Sorting Complexes Required for Transport/physiology ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Mi-2 Nucleosome Remodeling and Deacetylase Complex/physiology ; Mice ; Polycomb Repressive Complex 1 ; Repressor Proteins/physiology ; Stem Cells/cytology ; Transcription Factors/metabolism
Chemical Substances	Endosomal Sorting Complexes Required for Transport ; Repressor Proteins ; Transcription Factors ; Polycomb Repressive Complex 1 (EC 2.3.2.27) ; Mi-2 Nucleosome Remodeling and Deacetylase Complex (EC 3.5.1.98)
Language	English
Publishing date	2012-03-17
Publishing country	Austria
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	203083-4
ISSN	1432-0886 ; 0009-5915
ISSN (online)	1432-0886
ISSN	0009-5915
DOI	10.1007/s00412-012-0365-x
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Article ; Online: Establishment and Use of Mouse Haploid ES Cells.

Leeb, Martin / Perry, Anthony C F / Wutz, Anton

Current protocols in mouse biology

2015 Volume 5, Issue 2, Page(s) 155–185

Abstract: Haploid genetics has facilitated new insights into mammalian pathways and disease mechanisms. Most animal cells are diploid, and mammalian haploid cell cultures have remained elusive for a long time. Recent methodological progress has enabled the routine ...

Abstract	Haploid genetics has facilitated new insights into mammalian pathways and disease mechanisms. Most animal cells are diploid, and mammalian haploid cell cultures have remained elusive for a long time. Recent methodological progress has enabled the routine derivation of haploid stem cell lines from mammalian haploid embryos. Here we provide detailed protocols for the establishment, culture, and manipulation of parthenogenetic and androgenetic haploid embryonic stem cells from mouse embryos.
MeSH term(s)	Animals ; Cell Culture Techniques/methods ; Cell Separation/methods ; Cryopreservation/methods ; Embryonic Stem Cells/chemistry ; Embryonic Stem Cells/cytology ; Female ; Flow Cytometry ; Genetic Techniques ; Haploidy ; Mice/embryology ; Mice/genetics ; Mutagenesis ; Oocytes/chemistry ; Oocytes/cytology ; Staining and Labeling/methods
Language	English
Publishing date	2015-06-01
Publishing country	United States
Document type	Journal Article
ISSN	2161-2617
ISSN (online)	2161-2617
DOI	10.1002/9780470942390.mo140214
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