Linker Histone H1.2 Cooperates with Cul4A and PAF1 to Drive H4K31 Ubiquitylation-Mediated Transactivation
Kyunghwan Kim,
Bomi Lee,
Jaehoon Kim,
Jongkyu Choi,
Jin-Man Kim,
Yue Xiong,
Robert G. Roeder,
Woojin An
Affiliations
Kyunghwan Kim
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA
Bomi Lee
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA
Jaehoon Kim
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA
Jongkyu Choi
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA
Jin-Man Kim
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA
Yue Xiong
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Robert G. Roeder
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA
Woojin An
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA
Increasing evidence suggests that linker histone H1 can influence distinct cellular processes by acting as a gene-specific regulator. However, the mechanistic basis underlying such H1 specificity and whether H1 acts in concert with other chromatin-altering activities remain unclear. Here, we show that one of the H1 subtypes, H1.2, stably interacts with Cul4A E3 ubiquitin ligase and PAF1 elongation complexes and that such interaction potentiates target gene transcription via induction of H4K31ubiquitylation, H3K4me3, and H3K79me2. H1.2, Cul4A, and PAF1 are functionally cooperative because their individual knockdown results in the loss of the corresponding histone marks and the deficiency of target gene transcription. H1.2 interacts with the serine 2-phosphorylated form of RNAPII, and we argue that it recruits the Cul4A and PAF1 complexes to target genes by bridging the interaction between the Cul4A and PAF1 complexes. These data define an expanded role for H1 in regulating gene transcription and illustrate its dependence on the elongation competence of RNAPII.
