Loss of Pcgf5 Affects Global H2A Monoubiquitination but Not the Function of Hematopoietic Stem and Progenitor Cells.
Polycomb-group RING finger proteins (Pcgf1-Pcgf6) are components of Polycomb repressive complex 1 (PRC1)-related complexes that catalyze monoubiquitination of histone H2A at lysine 119 (H2AK119ub1), an epigenetic mark associated with repression of genes. Pcgf5 has been characterized as a component o...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4852895?pdf=render |
| _version_ | 1811319696956325888 |
|---|---|
| author | Sha Si Yaeko Nakajima-Takagi Kazumasa Aoyama Motohiko Oshima Atsunori Saraya Hiroki Sugishita Manabu Nakayama Tomoyuki Ishikura Haruhiko Koseki Atsushi Iwama |
| author_facet | Sha Si Yaeko Nakajima-Takagi Kazumasa Aoyama Motohiko Oshima Atsunori Saraya Hiroki Sugishita Manabu Nakayama Tomoyuki Ishikura Haruhiko Koseki Atsushi Iwama |
| author_sort | Sha Si |
| collection | DOAJ |
| description | Polycomb-group RING finger proteins (Pcgf1-Pcgf6) are components of Polycomb repressive complex 1 (PRC1)-related complexes that catalyze monoubiquitination of histone H2A at lysine 119 (H2AK119ub1), an epigenetic mark associated with repression of genes. Pcgf5 has been characterized as a component of PRC1.5, one of the non-canonical PRC1, consisting of Ring1a/b, Rybp/Yaf2 and Auts2. However, the biological functions of Pcgf5 have not yet been identified. Here we analyzed the impact of the deletion of Pcgf5 specifically in hematopoietic stem and progenitor cells (HSPCs). Pcgf5 is expressed preferentially in hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) compared with committed myeloid progenitors and differentiated cells. We transplanted bone marrow (BM) cells from Rosa::Cre-ERT control and Cre-ERT;Pcgf5fl/fl mice into lethally irradiated recipient mice. At 4 weeks post-transplantation, we deleted Pcgf5 by injecting tamoxifen, however, no obvious changes in hematopoiesis were detected including the number of HSPCs during a long-term observation period following the deletion. Competitive BM repopulating assays revealed normal repopulating capacity of Pcgf5-deficient HSCs. Nevertheless, Pcgf5-deficient HSPCs showed a significant reduction in H2AK119ub1 levels compared with the control. ChIP-sequence analysis confirmed the reduction in H2AK119ub1 levels, but revealed no significant association of changes in H2AK119ub1 levels with gene expression levels. Our findings demonstrate that Pcgf5-containing PRC1 functions as a histone modifier in vivo, but its role in HSPCs is limited and can be compensated by other PRC1-related complexes in HSPCs. |
| first_indexed | 2024-04-13T12:47:11Z |
| format | Article |
| id | doaj.art-50e380feea984cf4be1b9c6f1c4346c9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T12:47:11Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-50e380feea984cf4be1b9c6f1c4346c92022-12-22T02:46:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015456110.1371/journal.pone.0154561Loss of Pcgf5 Affects Global H2A Monoubiquitination but Not the Function of Hematopoietic Stem and Progenitor Cells.Sha SiYaeko Nakajima-TakagiKazumasa AoyamaMotohiko OshimaAtsunori SarayaHiroki SugishitaManabu NakayamaTomoyuki IshikuraHaruhiko KosekiAtsushi IwamaPolycomb-group RING finger proteins (Pcgf1-Pcgf6) are components of Polycomb repressive complex 1 (PRC1)-related complexes that catalyze monoubiquitination of histone H2A at lysine 119 (H2AK119ub1), an epigenetic mark associated with repression of genes. Pcgf5 has been characterized as a component of PRC1.5, one of the non-canonical PRC1, consisting of Ring1a/b, Rybp/Yaf2 and Auts2. However, the biological functions of Pcgf5 have not yet been identified. Here we analyzed the impact of the deletion of Pcgf5 specifically in hematopoietic stem and progenitor cells (HSPCs). Pcgf5 is expressed preferentially in hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) compared with committed myeloid progenitors and differentiated cells. We transplanted bone marrow (BM) cells from Rosa::Cre-ERT control and Cre-ERT;Pcgf5fl/fl mice into lethally irradiated recipient mice. At 4 weeks post-transplantation, we deleted Pcgf5 by injecting tamoxifen, however, no obvious changes in hematopoiesis were detected including the number of HSPCs during a long-term observation period following the deletion. Competitive BM repopulating assays revealed normal repopulating capacity of Pcgf5-deficient HSCs. Nevertheless, Pcgf5-deficient HSPCs showed a significant reduction in H2AK119ub1 levels compared with the control. ChIP-sequence analysis confirmed the reduction in H2AK119ub1 levels, but revealed no significant association of changes in H2AK119ub1 levels with gene expression levels. Our findings demonstrate that Pcgf5-containing PRC1 functions as a histone modifier in vivo, but its role in HSPCs is limited and can be compensated by other PRC1-related complexes in HSPCs.http://europepmc.org/articles/PMC4852895?pdf=render |
| spellingShingle | Sha Si Yaeko Nakajima-Takagi Kazumasa Aoyama Motohiko Oshima Atsunori Saraya Hiroki Sugishita Manabu Nakayama Tomoyuki Ishikura Haruhiko Koseki Atsushi Iwama Loss of Pcgf5 Affects Global H2A Monoubiquitination but Not the Function of Hematopoietic Stem and Progenitor Cells. PLoS ONE |
| title | Loss of Pcgf5 Affects Global H2A Monoubiquitination but Not the Function of Hematopoietic Stem and Progenitor Cells. |
| title_full | Loss of Pcgf5 Affects Global H2A Monoubiquitination but Not the Function of Hematopoietic Stem and Progenitor Cells. |
| title_fullStr | Loss of Pcgf5 Affects Global H2A Monoubiquitination but Not the Function of Hematopoietic Stem and Progenitor Cells. |
| title_full_unstemmed | Loss of Pcgf5 Affects Global H2A Monoubiquitination but Not the Function of Hematopoietic Stem and Progenitor Cells. |
| title_short | Loss of Pcgf5 Affects Global H2A Monoubiquitination but Not the Function of Hematopoietic Stem and Progenitor Cells. |
| title_sort | loss of pcgf5 affects global h2a monoubiquitination but not the function of hematopoietic stem and progenitor cells |
| url | http://europepmc.org/articles/PMC4852895?pdf=render |
| work_keys_str_mv | AT shasi lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells AT yaekonakajimatakagi lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells AT kazumasaaoyama lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells AT motohikooshima lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells AT atsunorisaraya lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells AT hirokisugishita lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells AT manabunakayama lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells AT tomoyukiishikura lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells AT haruhikokoseki lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells AT atsushiiwama lossofpcgf5affectsglobalh2amonoubiquitinationbutnotthefunctionofhematopoieticstemandprogenitorcells |