Tissue-specific mitotic bookmarking by hematopoietic transcription factor GATA1.
Tissue-specific transcription patterns are preserved throughout cell divisions to maintain lineage fidelity. We investigated whether transcription factor GATA1 plays a role in transmitting hematopoietic gene expression programs through mitosis when transcription is transiently silenced. Live-cell imaging revealed that a fraction of GATA1 is retained focally within mitotic chromatin. ChIP-seq of highly purified mitotic cells uncovered that key hematopoietic regulatory genes are occupied by GATA1 in mitosis. The GATA1 coregulators FOG1 and TAL1 dissociate from mitotic chromatin, suggesting that GATA1 functions as platform for their postmitotic recruitment. Mitotic GATA1 target genes tend to reactivate more rapidly upon entry into G1 than genes from which GATA1 dissociates. Mitosis-specific destruction of GATA1 delays reactivation selectively of genes that retain GATA1 during mitosis. These studies suggest a requirement of mitotic "bookmarking" by GATA1 for the faithful propagation of cell-type-specific transcription programs through cell division.
Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Stephan
S
Kadauke
Maheshi I
MI
Udugama
Jan M
JM
Pawlicki
Jordan C
JC
Achtman
Deepti P
DP
Jain
Yong
Y
Cheng
Ross C
RC
Hardison
Gerd A
GA
Blobel
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism; D041905:Erythroid Cells / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D006410:Hematopoiesis; D042421:Histone Code; D051379:Mice; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D050982:GATA1 Transcription Factor; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C494689:Gata1 protein, mouse; C489366:Tal1 protein, mouse; C107310:Zfpm1 protein, mouse