Generation of bivalent chromatin domains during cell fate decisions
<p>Abstract</p> <p>Background</p> <p>In self-renewing, pluripotent cells, bivalent chromatin modification is thought to silence (H3K27me3) lineage control genes while 'poising' (H3K4me3) them for subsequent activation during differentiation, implying an import...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-06-01
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| Series: | Epigenetics & Chromatin |
| Online Access: | http://www.epigeneticsandchromatin.com/content/4/1/9 |
| _version_ | 1818919383318134784 |
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| author | De Gobbi Marco Garrick David Lynch Magnus Vernimmen Douglas Hughes Jim R Goardon Nicolas Luc Sidinh Lower Karen M Sloane-Stanley Jacqueline A Pina Cristina Soneji Shamit Renella Raffaele Enver Tariq Taylor Stephen Jacobsen Sten Eirik W Vyas Paresh Gibbons Richard J Higgs Douglas R |
| author_facet | De Gobbi Marco Garrick David Lynch Magnus Vernimmen Douglas Hughes Jim R Goardon Nicolas Luc Sidinh Lower Karen M Sloane-Stanley Jacqueline A Pina Cristina Soneji Shamit Renella Raffaele Enver Tariq Taylor Stephen Jacobsen Sten Eirik W Vyas Paresh Gibbons Richard J Higgs Douglas R |
| author_sort | De Gobbi Marco |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>In self-renewing, pluripotent cells, bivalent chromatin modification is thought to silence (H3K27me3) lineage control genes while 'poising' (H3K4me3) them for subsequent activation during differentiation, implying an important role for epigenetic modification in directing cell fate decisions. However, rather than representing an equivalently balanced epigenetic mark, the patterns and levels of histone modifications at bivalent genes can vary widely and the criteria for identifying this chromatin signature are poorly defined.</p> <p>Results</p> <p>Here, we initially show how chromatin status alters during lineage commitment and differentiation at a single well characterised bivalent locus. In addition we have determined how chromatin modifications at this locus change with gene expression in both ensemble and single cell analyses. We also show, on a global scale, how mRNA expression may be reflected in the ratio of H3K4me3/H3K27me3.</p> <p>Conclusions</p> <p>While truly 'poised' bivalently modified genes may exist, the original hypothesis that all bivalent genes are epigenetically premarked for subsequent expression might be oversimplistic. In fact, from the data presented in the present work, it is equally possible that many genes that appear to be bivalent in pluripotent and multipotent cells may simply be stochastically expressed at low levels in the process of multilineage priming. Although both situations could be considered to be forms of 'poising', the underlying mechanisms and the associated implications are clearly different.</p> |
| first_indexed | 2024-12-20T01:04:59Z |
| format | Article |
| id | doaj.art-c82856337f104985994b59d99e7111f9 |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-12-20T01:04:59Z |
| publishDate | 2011-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-c82856337f104985994b59d99e7111f92022-12-21T19:58:53ZengBMCEpigenetics & Chromatin1756-89352011-06-0141910.1186/1756-8935-4-9Generation of bivalent chromatin domains during cell fate decisionsDe Gobbi MarcoGarrick DavidLynch MagnusVernimmen DouglasHughes Jim RGoardon NicolasLuc SidinhLower Karen MSloane-Stanley Jacqueline APina CristinaSoneji ShamitRenella RaffaeleEnver TariqTaylor StephenJacobsen Sten Eirik WVyas PareshGibbons Richard JHiggs Douglas R<p>Abstract</p> <p>Background</p> <p>In self-renewing, pluripotent cells, bivalent chromatin modification is thought to silence (H3K27me3) lineage control genes while 'poising' (H3K4me3) them for subsequent activation during differentiation, implying an important role for epigenetic modification in directing cell fate decisions. However, rather than representing an equivalently balanced epigenetic mark, the patterns and levels of histone modifications at bivalent genes can vary widely and the criteria for identifying this chromatin signature are poorly defined.</p> <p>Results</p> <p>Here, we initially show how chromatin status alters during lineage commitment and differentiation at a single well characterised bivalent locus. In addition we have determined how chromatin modifications at this locus change with gene expression in both ensemble and single cell analyses. We also show, on a global scale, how mRNA expression may be reflected in the ratio of H3K4me3/H3K27me3.</p> <p>Conclusions</p> <p>While truly 'poised' bivalently modified genes may exist, the original hypothesis that all bivalent genes are epigenetically premarked for subsequent expression might be oversimplistic. In fact, from the data presented in the present work, it is equally possible that many genes that appear to be bivalent in pluripotent and multipotent cells may simply be stochastically expressed at low levels in the process of multilineage priming. Although both situations could be considered to be forms of 'poising', the underlying mechanisms and the associated implications are clearly different.</p>http://www.epigeneticsandchromatin.com/content/4/1/9 |
| spellingShingle | De Gobbi Marco Garrick David Lynch Magnus Vernimmen Douglas Hughes Jim R Goardon Nicolas Luc Sidinh Lower Karen M Sloane-Stanley Jacqueline A Pina Cristina Soneji Shamit Renella Raffaele Enver Tariq Taylor Stephen Jacobsen Sten Eirik W Vyas Paresh Gibbons Richard J Higgs Douglas R Generation of bivalent chromatin domains during cell fate decisions Epigenetics & Chromatin |
| title | Generation of bivalent chromatin domains during cell fate decisions |
| title_full | Generation of bivalent chromatin domains during cell fate decisions |
| title_fullStr | Generation of bivalent chromatin domains during cell fate decisions |
| title_full_unstemmed | Generation of bivalent chromatin domains during cell fate decisions |
| title_short | Generation of bivalent chromatin domains during cell fate decisions |
| title_sort | generation of bivalent chromatin domains during cell fate decisions |
| url | http://www.epigeneticsandchromatin.com/content/4/1/9 |
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