Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes


ABSTRACT: We use ChIP-seq to discover the genome-wide sites of acetylation of lysine 56 of the histone H3 (H3K56), which is a target of three histone modifying enzymes with known roles in diabetes and insulin resistance, in human adipocytes derived from mesenchymal stem cells. Surprisingly, we find that a very large fraction of genes show some level of acetylation on H3K56, but the highest levels of acetylation are associated with genes previously reported to be involved in type 2 diabetes. Using computational methods, we propose that the transcription factor E2F4 may be involved in recruiting histone modifying enzymes to these sites. We confirm this prediction by measuring the binding of E2F4 using ChIP-seq. We also examine the binding of two other proteins using ChIP-Seq: HSF-1 and C/EBPM-NM-1M-BM- . HSF-1 is a master regulator of stress responses, and is a target of the same histone modifiers as H3K56. We find a high degree of overlap between HSF-1 binding and H3K56 acetylation even in cells that are not stressed. By contrast, C/EBPM-NM-1M-BM- , which is not known to be modified by these enzymes, shows much less overlap with the sites of H3K56 acetylation. Our results represent the first mapping of the regulatory code of human adipocytes. Examination of H3K56 acetylation sites and E2F4,C/EBPM-NM-1 and HSF-1 binding sites in human adipocytes.

ORGANISM(S): Homo sapiens

SUBMITTER: Kinyui Alice LO 

PROVIDER: E-GEOD-24326 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes.

Lo Kinyui Alice KA   Bauchmann Mary K MK   Baumann Amy P AP   Donahue Christopher J CJ   Thiede Mark A MA   Hayes Lisa S LS   des Etages Shelley Ann G SA   Fraenkel Ernest E  

PloS one 20110602 6


The growing epidemic of obesity and metabolic diseases calls for a better understanding of adipocyte biology. The regulation of transcription in adipocytes is particularly important, as it is a target for several therapeutic approaches. Transcriptional outcomes are influenced by both histone modifications and transcription factor binding. Although the epigenetic states and binding sites of several important transcription factors have been profiled in the mouse 3T3-L1 cell line, such data are lac  ...[more]

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