Bath: a Bayesian approach to analyze epigenetic transitions reveals a dual role of H3K27me3 in chondrogenesis
Abstract Background Histone modifications are key epigenetic regulators of cell differentiation and have been intensively studied in many cell types and tissues. Nevertheless, we still lack a thorough understanding of how combinations of histone marks at the same genomic location, so-called chromati...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13072-025-00594-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849471363231776768 |
|---|---|
| author | Christoph Neu Manuela Wuelling Christoph Waterkamp Daniel Hoffmann Andrea Vortkamp |
| author_facet | Christoph Neu Manuela Wuelling Christoph Waterkamp Daniel Hoffmann Andrea Vortkamp |
| author_sort | Christoph Neu |
| collection | DOAJ |
| description | Abstract Background Histone modifications are key epigenetic regulators of cell differentiation and have been intensively studied in many cell types and tissues. Nevertheless, we still lack a thorough understanding of how combinations of histone marks at the same genomic location, so-called chromatin states, are linked to gene expression, and how these states change in the process of differentiation. To receive insight into the epigenetic changes accompanying the differentiation along the chondrogenic lineage we analyzed two publicly available datasets representing (1) the early differentiation stages from embryonic stem cells into chondrogenic cells and (2) the direct differentiation of mature chondrocyte subtypes. Results We used ChromHMM to define chromatin states of 6 activating and repressive histone marks for each dataset and tracked the transitions between states that are associated with the progression of differentiation. As differentiation-associated state transitions are likely limited to a reduced set of genes, one challenge of such global analyses is the identification of these rare transitions within the large-scale data. To overcome this problem, we have developed a relativistic approach that quantitatively relates transitions of chromatin states on defined groups of tissue-specific genes to the background. In the early lineage, we found an increased transition rate into activating chromatin states on mesenchymal and chondrogenic genes while mature chondrocytes are mainly enriched in transition between activating states. Interestingly, we also detected a complex extension of the classical bivalent state (H3K4me3/H3K27me3) consisting of several activating promoter marks besides the repressive mark H3K27me3. Within the early lineage, mesenchymal and chondrogenic genes undergo transitions from this state into active promoter states, indicating that the initiation of gene expression utilizes this complex combination of activating and repressive marks. In contrast, at mature differentiation stages the inverse transition, the gain of H3K27me3 on active promoters, seems to be a critical parameter linked to the initiation of gene repression in the course of differentiation. Conclusions Our results emphasize the importance of a relative analysis of complex epigenetic data to identify chromatin state transitions associated with cell lineage progression. They further underline the importance of serial analysis of such transitions to uncover the diverse regulatory potential of distinct histone modifications like H3K27me3. |
| format | Article |
| id | doaj-art-6be378eaa2e14d58828a75792aee69b8 |
| institution | Kabale University |
| issn | 1756-8935 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj-art-6be378eaa2e14d58828a75792aee69b82025-08-20T03:24:52ZengBMCEpigenetics & Chromatin1756-89352025-06-0118111510.1186/s13072-025-00594-6Bath: a Bayesian approach to analyze epigenetic transitions reveals a dual role of H3K27me3 in chondrogenesisChristoph Neu0Manuela Wuelling1Christoph Waterkamp2Daniel Hoffmann3Andrea Vortkamp4Developmental Biology, University Duisburg-EssenDevelopmental Biology, University Duisburg-EssenBioinformatics and Computational Biophysics, University Duisburg-EssenBioinformatics and Computational Biophysics, University Duisburg-EssenDevelopmental Biology, University Duisburg-EssenAbstract Background Histone modifications are key epigenetic regulators of cell differentiation and have been intensively studied in many cell types and tissues. Nevertheless, we still lack a thorough understanding of how combinations of histone marks at the same genomic location, so-called chromatin states, are linked to gene expression, and how these states change in the process of differentiation. To receive insight into the epigenetic changes accompanying the differentiation along the chondrogenic lineage we analyzed two publicly available datasets representing (1) the early differentiation stages from embryonic stem cells into chondrogenic cells and (2) the direct differentiation of mature chondrocyte subtypes. Results We used ChromHMM to define chromatin states of 6 activating and repressive histone marks for each dataset and tracked the transitions between states that are associated with the progression of differentiation. As differentiation-associated state transitions are likely limited to a reduced set of genes, one challenge of such global analyses is the identification of these rare transitions within the large-scale data. To overcome this problem, we have developed a relativistic approach that quantitatively relates transitions of chromatin states on defined groups of tissue-specific genes to the background. In the early lineage, we found an increased transition rate into activating chromatin states on mesenchymal and chondrogenic genes while mature chondrocytes are mainly enriched in transition between activating states. Interestingly, we also detected a complex extension of the classical bivalent state (H3K4me3/H3K27me3) consisting of several activating promoter marks besides the repressive mark H3K27me3. Within the early lineage, mesenchymal and chondrogenic genes undergo transitions from this state into active promoter states, indicating that the initiation of gene expression utilizes this complex combination of activating and repressive marks. In contrast, at mature differentiation stages the inverse transition, the gain of H3K27me3 on active promoters, seems to be a critical parameter linked to the initiation of gene repression in the course of differentiation. Conclusions Our results emphasize the importance of a relative analysis of complex epigenetic data to identify chromatin state transitions associated with cell lineage progression. They further underline the importance of serial analysis of such transitions to uncover the diverse regulatory potential of distinct histone modifications like H3K27me3.https://doi.org/10.1186/s13072-025-00594-6Epigenetic regulationHistone modificationChondrocyte differentiationChromatin states |
| spellingShingle | Christoph Neu Manuela Wuelling Christoph Waterkamp Daniel Hoffmann Andrea Vortkamp Bath: a Bayesian approach to analyze epigenetic transitions reveals a dual role of H3K27me3 in chondrogenesis Epigenetics & Chromatin Epigenetic regulation Histone modification Chondrocyte differentiation Chromatin states |
| title | Bath: a Bayesian approach to analyze epigenetic transitions reveals a dual role of H3K27me3 in chondrogenesis |
| title_full | Bath: a Bayesian approach to analyze epigenetic transitions reveals a dual role of H3K27me3 in chondrogenesis |
| title_fullStr | Bath: a Bayesian approach to analyze epigenetic transitions reveals a dual role of H3K27me3 in chondrogenesis |
| title_full_unstemmed | Bath: a Bayesian approach to analyze epigenetic transitions reveals a dual role of H3K27me3 in chondrogenesis |
| title_short | Bath: a Bayesian approach to analyze epigenetic transitions reveals a dual role of H3K27me3 in chondrogenesis |
| title_sort | bath a bayesian approach to analyze epigenetic transitions reveals a dual role of h3k27me3 in chondrogenesis |
| topic | Epigenetic regulation Histone modification Chondrocyte differentiation Chromatin states |
| url | https://doi.org/10.1186/s13072-025-00594-6 |
| work_keys_str_mv | AT christophneu bathabayesianapproachtoanalyzeepigenetictransitionsrevealsadualroleofh3k27me3inchondrogenesis AT manuelawuelling bathabayesianapproachtoanalyzeepigenetictransitionsrevealsadualroleofh3k27me3inchondrogenesis AT christophwaterkamp bathabayesianapproachtoanalyzeepigenetictransitionsrevealsadualroleofh3k27me3inchondrogenesis AT danielhoffmann bathabayesianapproachtoanalyzeepigenetictransitionsrevealsadualroleofh3k27me3inchondrogenesis AT andreavortkamp bathabayesianapproachtoanalyzeepigenetictransitionsrevealsadualroleofh3k27me3inchondrogenesis |