News archives


OCTOBER - DECEMBER 17

JULY - SEPTEMBER 17

APRIL - JUNE 17

JANUARY - MARCH 17

OCTOBER - DECEMBER 16

JULY - SEPTEMBER 16

APRIL - JUNE 16

JANUARY - MARCH 16

OCTOBER - DECEMBER 15

JULY - SEPTEMBER 15

APRIL - JUNE 15

JANUARY - MARCH 15

OCTOBER - DECEMBER 14

JULY - SEPTEMBER 14

APRIL - JUNE 14

JANUARY - MARCH 14

OCTOBER - DECEMBER 13

JULY - SEPTEMBER 13

APRIL - JUNE 13

JANUARY - MARCH 13

OCTOBER - DECEMBER 12

JULY - SEPTEMBER 12

APRIL - JUNE 12

JANUARY - MARCH 12

OCTOBER - DECEMBER 11

JULY - SEPTEMBER 11

APRIL - JUNE 11

JANUARY - MARCH 11

OCTOBER - DECEMBER 10

JULY - SEPTEMBER 10

APRIL - JUNE 10

JANUARY - MARCH 10

OCTOBER - DECEMBER 09

JULY - SEPTEMBER 09

APRIL - JUNE 09

JANUARY - MARCH 09

OCTOBER - DECEMBER 08

JULY - SEPTEMBER 08

APRIL - JUNE 08

JANUARY - MARCH 08

OCTOBER - DECEMBER 07

JULY - SEPTEMBER 07

APRIL - JUNE 07

JANUARY - MARCH 07

 
  current news   Press   selected story    
     
  13 June 2014  
  Chromatin and Transcription Transitions of Mammalian Adult Germline Stem Cells and Spermatogenesis
 
 



Authors
Saher Sue Hammoud1,4, Diana Low2,3, Chongil Yi1, Douglas T. Carrell4, Ernesto Guccione*2,3 and Bradley R. Cairns*1

1    Howard Hughes Medical Institute, Department of Oncological Sciences, and Huntsman Cancer       Institute, University of Utah School of Medicine, Salt Lake City, UT 84112
2    Division of Cancer Genetics and Therapeutics, Laboratory of Chromatin, Epigenetics &       Differentiation, Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science,       Technology and Research), Singapore 138673
3    Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore       Singapore 119074
4    Department of Surgery (Urology), Obstetrics and Gynecology, and Human Genetics, University of       Utah School of Medicine, Salt Lake City, Utah, USA

*    Corresponding author

Published on line in Cell Stem Cell on 15 May 2014. .

Abstract

Adult germline stem cells (AGSCs) self-renew (Thy1+ enriched) or commit to gametogenesis (Kit+ enriched). To better understand how chromatin regulates AGSC biology and gametogenesis, we derived stage-specific high-resolution profiles of DNA methylation, 5hmC, histone modifications/variants, and RNA-seq in AGSCs and during spermatogenesis. First, we define striking signaling and transcriptional differences between AGSC types, involving key self-renewal and proliferation pathways. Second, key pluripotency factors (e.g., Nanog) are silent in AGSCs and bear particular chromatin/DNAme attributes that may “poise” them for reactivation after fertilization. Third, AGSCs display chromatin “poising/bivalency” of enhancers and promoters for embryonic transcription factors. Remarkably, gametogenesis occurs without significant changes in DNAme and instead involves transcription of DNA-methylated promoters bearing high RNAPol2, H3K9ac, H3K4me3, low CG content, and (often) 5hmC. Furthermore, key findings were confirmed in human sperm. Here, we reveal AGSC signaling asymmetries and chromatin/DNAme strategies in AGSCs to poise key transcription factors and to activate DNA-methylated promoters during gametogenesis.

Figure Legend: Summary schematic of transcription and chromatin transitions within the germ cell cycle


For more information on Ernesto Guccione’s laboratory, please click here.