Drosophila CP190- and dCTCF-mediated enhancer blocking is augmented by SUMOylation

Abstract

BackgroundChromatin insulators shield promoters and chromatin domains from neighboring enhancers or chromatin regions with opposing activities. Insulator-binding proteins and their cofactors mediate the boundary function. In general, covalent modification of proteins by the small ubiquitin-like modifier (SUMO) is an important mechanism to control the interaction of proteins within complexes.ResultsHere we addressed the impact of dSUMO in respect of insulator function, chromatin binding of insulator factors and formation of insulator speckles in Drosophila. SUMOylation augments the enhancer blocking function of four different insulator sequences and increases the genome-wide binding of the insulator cofactor CP190.ConclusionsThese results indicate that enhanced chromatin binding of SUMOylated CP190 causes fusion of insulator speckles, which may allow for more efficient insulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-017-0140-6) contains supplementary material, which is available to authorized users.

SUMO and Transcriptional Regulation: The Lessons of Large-Scale Proteomic, Modifomic and Genomic Studies

“…Along the same line, at least two protein components (Mod(mdg4) and CP190) of the Drosophila melanogaster gypsy insulator are SUMOylated, which attenuates chromatin insulator activity [ 275 ]. SUMOylation is necessary for these insulator proteins to colocalize in nuclear speckles named insulator bodies [ 276 ], as well as for enhancer blocking [ 277 ]. SUMOylation of drosophila CTCF (dCTCF) plays the same role [ 277 ].…”

“…SUMOylation is necessary for these insulator proteins to colocalize in nuclear speckles named insulator bodies [ 276 ], as well as for enhancer blocking [ 277 ]. SUMOylation of drosophila CTCF (dCTCF) plays the same role [ 277 ]. Also worth of mention, PIAS1-dependent SUMOylation of the MAR-associated SATB2 protein was shown to modulate the expression of the immunoglobulin µ gene in preB cells through enhancing association of the µ immunoglobulin locus with MARs [ 278 ].…”

DeSUMOylation of chromatin-bound proteins limits the rapid transcriptional reprogramming induced by daunorubicin in acute myeloid leukemias

“…Second, heat shock was shown to induce a transient depletion of SUMOylated proteins from CTCF-bound sites in intergenic regions and their relocation at promoters of transcribed genes ( 24 ). Third, SUMOylated proteins were found enriched at CTCF-bound sites in Drosophila and associated to enhancer blocking ( 85 ). Along this line, we found that the CTCF-binding site is the most enriched motif in SUMO-2/3 bound chromatin regions in AML cells and CUT&RUN experiments with CTCF antibodies confirmed that the co-binding of CTCF and SUMO is highly enriched at promoters and enhancers compared to intergenic regions.…”

SUMOylation controls the rapid transcriptional reprogramming induced by anthracyclines in Acute Myeloid Leukemias

“…Second, heat shock was shown to induce a transient depletion of SUMOylated proteins from CTCF-bound sites in intergenic regions and their relocation at promoters of transcribed genes (24). Third, SUMOylated proteins were found enriched at CTCF-bound sites in Drosophila and associated to enhancer blocking (71). Along this line, we found that the CTCF-binding site is the most enriched motif in SUMO-2/3 bound chromatin regions in AML cells and the co-binding of CTCF and SUMO is highly enriched at promoter and enhancers compared to intergenic regions.…”