About this item:

16 Views | 3 Downloads

Author Notes:

Corresponding author. Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-5622, USA. Tel.: +1 734 647 2124; fax: +1 734 647 9523. jeschwar@umich.edu (J. Schwartz).

The authors thank Drs. Jindan Yu and Hong Cheng, and the University of Michigan Sequencing Core for their assistance in ChIP-Seq experiment design and sample preparation; and Jennifer Harley and Aaron Taylor for technical assistance.

Subjects:

Research Funding:

This work was supported by grants to JS from NIH (DK46072), the American Diabetes Association (7-09-BS-168) and Center for Genetics in Health and Medicine at University of Michigan; and by NIH grant HG005119 to ZSQ.

GL was supported by NIH T32 GM07315, Director’s and Loeb Fellowships from University of Michigan Cancer Center and by a Rackham Predoctoral Fellowship, University of Michigan.

CRL was supported by a postdoctoral fellowship from the Center Q6 for Organogenesis (NIH T32 HD007505) at University of Michigan.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • Endocrinology & Metabolism
  • Socs2
  • Cish
  • Co-activator
  • Co-repressor
  • Adipocytes
  • ChIP-Seq
  • B-CELL LYMPHOMA
  • PANCREATIC BETA-CELLS
  • BINDING-PROTEIN-BETA
  • HISTONE-DEACETYLASE
  • IN-VIVO
  • NUCLEAR RECEPTOR
  • REGULATED TRANSCRIPTION
  • TRANSACTIVATION DOMAIN
  • PROTOONCOGENE BCL-6
  • CHROMATIN-STRUCTURE

Reciprocal occupancy of BCL6 and STAT5 on Growth Hormone target genes: contrasting transcriptional outcomes and promoter-specific roles of p300 and HDAC3

Tools:

Journal Title:

Molecular and Cellular Endocrinology

Volume:

Volume 395, Number 1-2

Publisher:

, Pages 19-31

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Expression of the Growth Hormone (GH)-stimulated gene Socs2 (Suppressor of Cytokine Signaling 2) is mediated by the transcription activator STAT5 (Signal Transducer and Activator of Transcription 5) and the transcription repressor BCL6 (B-Cell Lymphoma 6). ChIP-Sequencing identified Cish (Cytokine-Inducible SH2-containing protein) and Bcl6 as having similar patterns of reciprocal occupancy by BCL6 and STAT5 in response to GH, though GH stimulates Cish and inhibits Bcl6 expression. The co-activator p300 occupied Socs2, Cish and Bcl6 promoters, and enhanced STAT5-mediated activation of Socs2 and Cish. In contrast, on Bcl6, p300 functioned as a repressor and inhibited in conjunction with STAT5 or BCL6. The co-repressor HDAC3 (Histone deacetylase 3) inhibited the Socs2, Cish and Bcl6 promoters in the presence of STAT5. Thus transcriptional outcomes on GH-regulated genes occupied by BCL6 and STAT5 are determined in a promoter-specific fashion by co-regulatory proteins which mediate the distinction between activating and repressive transcription factors.

Copyright information:

© 2014 Elsevier Ireland Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote