U.S. flag

An official website of the United States government

Here’s how you know
Here’s how you know

**Official websites use .gov**
A **.gov** website belongs to an official government organization in the United States.

**Secure .gov websites use HTTPS**
A **lock** ( A locked padlock) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.
Search Query:
			MAIN MENU

																				
              Health Topics
								All Health Topics A-Z
					
													
		

		Asthma


				

															Heart-Healthy Living


				

															High Blood Pressure


				

															Sickle Cell Disease


				

															Sleep Apnea


				

															Information & Resources on COVID-19
																				
              Health Education
								Education Programs and Initiatives
					
													
		

		The Heart Truth®


				

															Learn More Breathe Better®


				

															Blood Diseases and Disorders Education Program


				

															Publications and Resources
																				
              The Science
								Research Focus Areas
					
													
		

		Blood Disorders and Blood Safety


				

															Sleep Science and Sleep Disorders


				

															Lung Diseases


				

															Health Disparities and Inequities


				

															Heart and Vascular Diseases


				

															Precision Medicine Activities


				

															Obesity, Nutrition, and Physical Activity


				

															Population and Epidemiology Studies


				

															Women’s Health


				

															Research Topics


				

															Clinical Trials


				

															All Science A-Z
																				
              Grants and Training
								Grants and Training Home


				

															Policies and Guidelines


				

															Funding Opportunities and Contacts


				

															Training and Career Development
																				
              News and Events
								News and Events Home
					
													
		

		Email Alerts


				

															All News
					
													
		

		NHLBI News


				

															NHLBI in the Press


				

															Research Features


				

															All Events
					
													
		

		Past Events


				

															Upcoming Events
																				
              About NHLBI
								About NHLBI Home
					
													
		

		Mission and Strategic Vision


				

															Leadership


				

															Divisions, Offices and Centers


				

															Advisory Committees


				

															Budget and Legislative Information


				

															Jobs and Working at the NHLBI


				

															Contact and FAQs


				

															NIH Sleep Research Plan
						
						HOME
		Search Text: Home/< Back ToThe Science/Epigenome Biology
  Epigenome Biology
    To study epigenetic mechanisms of development and differentiation across the mammalian genome, the Laboratory of Epigenome Biology, led by Dr. Keji Zhao, wanted a comprehensive and unbiased approach that would avoid the selection bias inherent in synthesizing probes for DNA microarrays.
    On This Page
    
          Keji Zhao
  Keji Zhao, Ph.D.
          NIH Distinguished Investigator
          Email
      Meet the Team
            Contact us
  Senior Investigator Research Interests
            
  Research Interests
              To study epigenetic mechanisms of development and differentiation across the mammalian genome, Dr. Zhao wanted a comprehensive and unbiased approach that would avoid the selection bias inherent in synthesizing probes for DNA microarrays. He and his colleagues therefore developed novel sequencing-based methods to study the epigenome, such as ChIP-Seq, which combines chromatin immunoprecipitation (ChIP) with the Next Generation Sequencing technique, and micrococcal nuclease sequencing (MNase-Seq). In addition they developed accompanying computational strategies to analyze the wealth of resulting sequence data. These tools are now widely applied in laboratories around the world.His laboratory applies these techniques to mapping epigenomes in hematopoietic cell lineages. In the first comprehensive description of a human epigenome, Dr. Zhao and his colleagues showed that different genomic regions in human CD4+ T cells were associated with histone methylation and acetylation patterns that differentially marked enhancers, promoters, and gene body regions of transcribed or silenced genes.Their findings displaced the simple model that histone deacetylases (HDAC) are bound to repressed genes while histone acetylases (HAT) are bound to active genes. Using a genome-wide approach, Dr. Zhao and his colleagues discovered that HDACs are also highly enriched at active genes whereas in silenced genes, both HATs and HDACs are bound at low levels. They found that inhibitors of HDACs prompted much higher acetylation levels at both inactive genes and active genes. This led to the hypothesis that HDACs operate dynamically to reset chromatin after RNA polymerase II directs transcriptional elongation at active genes, whereas HDACs and HATs function together to maintain inactive genes at a poised state that can be induced rapidly in response to environmental cues.Dr. Zhao also provided the first genome-wide description of nucleosome positioning in the mammalian genome, describing the location of nucleosomes relative to transcriptional start sites in CD4+ T cells and demonstrating extensive nucleosome reorganization in promoters and enhancers following T cell receptor signaling.Using the tools he has pioneered, Dr. Zhao has built a schema of modifications associated with particular areas of the genome; now, he wants to understand how they are regulated and how regulatory mechanisms contribute to processes like cellular memory, differentiation, and pathology. His laboratory is studying how the interplay between transcription factors and various chromatin modifying enzymes, including both histone modifying enzymes and ATP-dependent chromatin remodeling complexes, regulates the dynamic epigenomic landscapes in various hematopoietic lineages. Dr. Zhao is also investigating how epigenome dynamics regulate memory and function during differentiation of induced pluripotent stem (iPS) cells and hematopoietic stem cells to various blood lineages.Additionally, Dr. Zhao is looking beyond two-dimensional relationships in the genome that regulate gene expression. It is known that the position of a specific gene in the nucleus is important for its regulation and expression—for example, evidence in yeast suggests that genes located at the nuclear periphery are repressed. Dr. Zhao aims to understand the three-dimensional organization of the nucleus as it relates to gene expression.
  Featured Publications
                O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β.
            Authors:Resto M, Kim BH, Fernandez AG, Abraham BJ, Zhao K, Lewis B
                                                                                                                        
            J Biol Chem
      
                2016 Oct 21;291(43):22703-22713
        Read Publication
                      Looping around Bcl6 in Germinal Center to Sharpen B Cell Immunity.
            Authors:Hu G, Zhao
                                                                                                                        
            Immunity
      
                2016 Sep 20;45(3):459-61
        Read Publication
                      Setd1a and NURF mediate chromatin dynamics and gene regulation during erythroid lineage commitment and differentiation.
            Authors:Li Y, Schulz VP, Deng C, Li G, Shen Y, Tusi BK, Ma G, Stees J, Qiu Y, Steiner LA, Zhou L, Zhao K, Bungert J, Gallagher PG, Huang
                                                                                                                        
            Nucleic Acids Res
      
                2016 Sep 06;44(15):7173-88
        Read Publication
                      Global intron retention mediated gene regulation during CD4+ T cell activation.
            Authors:Ni T, Yang W, Han M, Zhang Y, Shen T, Nie H, Zhou Z, Dai Y, Yang Y, Liu P, Cui K, Zeng Z, Tian Y, Zhou B, Wei G, Zhao K, Peng W, Zhu
                                                                                                                        
            Nucleic Acids Res
      
                2016 Aug 19;44(14):6817-29
        Read Publication
                      Lineage relationship of CD8(+) T cell subsets is revealed by progressive changes in the epigenetic landscape.
            Authors:Crompton JG, Narayanan M, Cuddapah S, Roychoudhuri R, Ji Y, Yang W, Patel SJ, Sukumar M, Palmer DC, Peng W, Wang E, Marincola FM, Klebanoff CA, Zhao K, Tsang JS, Gattinoni L, Restifo N
                                                                                                                        
            Cell Mol Immunol
      
                2016 Jul 01;13(4):502-13
        Read Publication
  Meet the Team

    Keji Zhao

            Keji Zhao, Ph.D.
                NIH Distinguished Investigator
                Keji Zhao received his undergraduate degree from Changwei Normal College in Weifang, China in 1980, his M.S. degree from Northeast Normal University in Changchun, China in 1985, and his Ph.D. from the University of Geneva, Switzerland in 1996. He was a Damon Runyon-Walter Winchel Cancer Research postdoctoral fellow at Stanford University in the laboratory of Gerald Crabtree. Dr. Zhao joined the NHLBI in 1999 and was appointed a Senior Investigator in 2007 and the Director of the Systems Biology Center in 2011. He received the NIH Director’s Award in recognition of innovative contributions that have provided novel insights into epigenetic control of gene expression in 2011 and NIH Merit Awards in 2007 and 2008. Dr. Zhao also received an APAO Award for Significant Accomplishments in Biomedical Research in 2008 and was elected a Fellow of the American Association for the Advancement of Science in 2012. Dr. Zhao has authored or coauthored more than 100 papers and book chapters. He is on the editorial boards of Genome Research and Cell & Bioscience.
    
          Contact the lab
    10 Center DrBethesda, MD 20814United States
        Phone:
                    301-496-2098
                Fax:
            301-402-1443
  Kidder
    
            Benjamin Kidder
        

    Research Fellow

        kidderbl@mail.nih.gov
            Kairong Cui
    
            Kairong Cui
        

    Staff Scientist

        cuik@mail.nih.gov
            Blank Avatar
    
            Alika Maunakea
        

    Special Volunteer

        alika.maunakea@nih.gov
            Blank Avatar
    
            Weiqun Peng
        

    Special Volunteer

        pengw@mail.nih.gov
            Brian Abraham
    
            Brian Abraham
        

    Special Volunteer

        abrahamb2@mail.nih.gov
            Qingsong Tang
    
            Qingsong Tang
        

    Biologist

        tangq@mail.nih.gov
            GangqingHu
    
            Gangqing Hu
        

    Postdoctoral Fellow

        hug21@mail.nih.gov
            Kraushaar
    
            Daniel Kraushaar
        

    Research Fellow

        daniel.kraushaar@nih.gov
            Blank Avatar
    
            Vivienne Chen
        

    Special Volunteer

        vivienne.chen@nih.gov
            Blank Avatar
    
            Gang Ren
        

    Graduate Student

        reng@mail.nih.gov
            Kelly Adams
    
            Kelly Adams
        

    Program Support Assistant

        adamskm2@mail.nih.gov
            Blank Avatar
    
            Misook Ha
        

    Special Volunteer

        misook.ha@nih.gov
            Chepelev
    
            Louri Chepelev
        

    Staff Scientist

        chepelevi@mail.nih.gov
            Northrup
    
            Daniel Northrup
        

    Postdoctoral Fellow

        northrupd@mail.nih.gov
            Placek
    
            Katarzyna Placek
        

    Postdoctoral Fellow

        placekk2@mail.nih.gov
                    Load more members
  Join Our Lab
    Join Our Lab

        There are no current openings.
                  Please check back soon. Back To Top Link
  

        

        Back to top
  Web Policies & Notices
  

        

              Accessibility
                      No FEAR Act Data
                      Privacy Policy
                      Freedom of Information Act (FOIA)
                      HHS Vulnerability Disclosure
    
          Related Government Websites
  

        

              Health and Human Services
                      National Institutes of Health
                      Office of the Inspector General
                      USA.gov
    
          Stay Connected
    
      
            chat bubblesLive ChatLive Chat with us, Monday through Friday, 8:30 a.m. to 5:00 p.m. EST.envelopeGet Email AlertsReceive automatic alerts about NHLBI related news and highlights from across the Institute.
  Footer Bottom
  

        



Contact Us
                            Site Index
                            Jobs