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Chromatin Repressive Complexes in Stem Cells, Development, and Cancer

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1 Chromatin Repressive Complexes in Stem Cells, Development, and Cancer
Anne Laugesen, Kristian Helin  Cell Stem Cell  Volume 14, Issue 6, Pages (June 2014) DOI: /j.stem Copyright © 2014 Elsevier Inc. Terms and Conditions

2 Figure 1 Schematic Representation of Polycomb Repressive Complexes
PRC2 catalyzes methylation of H3K27 (red circles). Several publications have shown that PRC2 recruitment relies on interacting proteins (such as JARID2, AEBP2, and PCL1-3), transient interactions with cell-type-specific transcription factors or noncoding RNAs. Canonical (CBX-containing) PRC1 complexes are recruited (dashed arrow) to H3K27me3, while noncanonical (PRC2-independent) PRC1 is recruited (dashed arrow) to CpG islands (blue circles) by KDM2B. Both CBX-containing and PRC2-independent PRC1 complexes catalyze the ubiquitylation of H2AK119 (red hexagons). Cell Stem Cell  , DOI: ( /j.stem ) Copyright © 2014 Elsevier Inc. Terms and Conditions

3 Figure 2 Schematic Representation of HDAC1- and HDAC2-Containing Complexes HDAC1 and HDAC2 of SIN3, NuRD, and CoREST catalyze the removal of acetyl groups from histone tails (green triangles). The NuRD subunits CHD3/4 are ATP-dependent chromatin remodelers and LSD1 present in CoREST (and possibly also NuRD) catalyzes demethylation of H3K4me1/2 (green circles). Recruitment of HDAC1- and HDAC2-containing complexes is thought to rely on chromatin-binding domains within each complex or additional interaction partners (not depicted). Cell Stem Cell  , DOI: ( /j.stem ) Copyright © 2014 Elsevier Inc. Terms and Conditions

4 Figure 3 Chromatin Sets Thresholds for Gene Activation Controlling Cell Identity (A) The chromatin environment sets thresholds for gene activation, ensuring that persistent exposure to appropriate signals (e.g., increasing transcription factor levels) is required for transcriptional activation. Loss of chromatin repressive complexes (dashed line) lowers the threshold and increases transcriptional noise. (B) Changes in chromatin thresholds in turn alter the barriers against changes in cell identity mediated by extrinsic (e.g., growth factors or hormones) and intrinsic (e.g., transcription factor levels or somatic mutations) signals. The biological outcome (whether the barriers are increased or decreased) depends on which genes become aberrantly activated by the loss of chromatin repressive complexes (dashed lines). For instance, if a repressive complex acts to limit the expression of an oncogene, loss of the complex would promote oncogenesis. Conversely, if the complex binds a tumor suppressor, its loss would increase the barrier for oncogenic transformation. Thus, loss of a chromatin repressive complex can influence cell identity in different directions, depending on the genes they regulate and the integration of the combined signals the affected cell receives. Cell Stem Cell  , DOI: ( /j.stem ) Copyright © 2014 Elsevier Inc. Terms and Conditions


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