Pathology & Laboratory Medicine

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Laboratory of Epigenetics and Genomic Integrity

Jessica Tyler, PhD, Principal Investigator

Dr. Tyler’s laboratory focuses on discovering the mechanistic basis of the epigenetic regulation of aging, genomic integrity and gene expression. Our studies use a combination of molecular genetics in budding yeast, tissue culture studies, biochemistry and next generation sequencing approaches. The proteins and processes that we study are so fundamentally conserved through eukaryotic evolution, that we can take advantage of the strengths of the highly genetically malleable yeast system to guide our studies in human cells. In addition to learning how chromatin regulates fundamental processes in the cell, our studies are helping us to understand how defects in the chromatin structure lead to gene dysfunction and genomic instability, in turn causing aging and disease states including cancer.

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Active Projects

  • Role of chromatin structure in maintaining genomic stability
  • Attaining longevity via chromatin dynamics
  • Discovering the mechanism of chromatin assembly

Active Grants

  • Discovering the molecular mechanisms that determine replicative lifespan
    PI: Jessica Tyler, PhD
    National Institutes of Health (NIH) Research Grant
  • Chromatin’s Role in the Repair of Radiation-induced Damage
    PI: Jessica Tyler, PhD
    National Cancer Institute (NIH)

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Selected Publications

The BRCA1-interacting protein Abraxas is required for genomic stability and tumor suppression

Jessica K. Tyler, PhD

The BRCA1-interacting protein Abraxas is required for genomic stability and tumor suppression

Cell Rep. 2014 Aug 7;8(3):807-17.

Castillo A, Paul A, Sun B, Huang TH, Wang Y, Yazinski SA, Tyler J, Li L, You MJ, Zou L, Yao J, Wang B.

PMID: 25066119; PMCID: PMC4149256.

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Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair

Jessica K. Tyler, PhD

Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair

Cell. 2008 Jul 25;134(2):231-43.

Chen CC, Carson JJ, Feser J, Tamburini B, Zabaronick S, Linger J, Tyler JK.

PMID: 18662539; PMCID: PMC2610811

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MOF phosphorylation by ATM regulates 53BP1-mediated double-strand break repair pathway choice

Jessica K. Tyler, PhD

MOF phosphorylation by ATM regulates 53BP1-mediated double-strand break repair pathway choice

Cell Rep. 2014 Jul 10;8(1):177-89.

Gupta A, Hunt CR, Hegde ML, Chakraborty S, Chakraborty S, Udayakumar D, Horikoshi N, Singh M, Ramnarain DB, Hittelman WN, Namjoshi S, Asaithamby A, Hazra TK, Ludwig T, Pandita RK, Tyler JK, Pandita TK.

Erratum in: Cell Rep. 2014 Jul 10;8(1):319.

PMID: 24953651; PMCID: PMC4300955.

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The conformational flexibility of the C-terminus of histone H4 promotes histone octamer and nucleosome stability and yeast viability

Jessica K. Tyler, PhD

The conformational flexibility of the C-terminus of histone H4 promotes histone octamer and nucleosome stability and yeast viability

Epigenetics Chromatin. 2012 Apr 27;5(1):5.

Chavez MS, Scorgie JK, Dennehey BK, Noone S, Tyler JK, Churchill ME.

PMID: 22541333; PMCID: PMC3439350

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Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation

Jessica K. Tyler, PhD

Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation

Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):E1072-81.

Das C, Roy S, Namjoshi S, Malarkey CS, Jones DN, Kutateladze TG, Churchill ME, Tyler JK.

PMID: 24616510; PMCID: PMC3970516

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Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging

Jessica K. Tyler, PhD

Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging

Genes Dev. 2014 Feb 15;28(4):396-408.

Hu Z, Chen K, Xia Z, Chavez M, Pal S, Seol JH, Chen CC, Li W, Tyler JK.

PMID: 24532716; PMCID: PMC3937517

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Mitotic phosphorylation of histone H3 threonine 80

Jessica K. Tyler, PhD

Mitotic phosphorylation of histone H3 threonine 80

Cell Cycle. 2014;13(3):440-52.

Hammond SL, Byrum SD, Namjoshi S, Graves HK, Dennehey BK, Tackett AJ, Tyler JK.

PMID: 24275038; PMCID: PMC3956540

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The C terminus of the histone chaperone Asf1 cross-links to histone H3 in yeast and promotes interaction with histones H3 and H4

Jessica K. Tyler, PhD

The C terminus of the histone chaperone Asf1 cross-links to histone H3 in yeast and promotes interaction with histones H3 and H4

Mol Cell Biol. 2013 Feb;33(3):605-21.

Dennehey BK, Noone S, Liu WH, Smith L, Churchill ME, Tyler JK.

PMID: 23184661; PMCID: PMC3666882

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DANPOS: dynamic analysis of nucleosome position and occupancy by sequencing

Jessica K. Tyler, PhD

DANPOS: dynamic analysis of nucleosome position and occupancy by sequencing

Genome Res. 2013 Feb;23(2):341-51.

Chen K, Xi Y, Pan X, Li Z, Kaestner K, Tyler J, Dent S, He X, Li W.

PMID: 23193179; PMCID: PMC3561875

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Elevated histone expression promotes life span extension

Jessica K. Tyler, PhD

Elevated histone expression promotes life span extension

Mol Cell. 2010 Sep 10;39(5):724-35.

Feser J, Truong D, Das C, Carson JJ, Kieft J, Harkness T, Tyler JK.

PMID: 20832724; PMCID: PMC3966075

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Chaperoning histones during DNA replication and repair

Jessica K. Tyler, PhD

Chaperoning histones during DNA replication and repair

Cell. 2010 Jan 22;140(2):183-95.

Ransom M, Dennehey BK, Tyler JK. 

PMID: 20141833; PMCID: PMC3433953

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CBP/p300-mediated acetylation of histone H3 on lysine 56

Jessica K. Tyler, PhD

CBP/p300-mediated acetylation of histone H3 on lysine 56

Nature. 2009 May 7;459(7243):113-7.

Das C, Lucia MS, Hansen KC, Tyler JK.

Erratum in: Nature. 2009 Aug 27;460(7259):1164.

PMID: 19270680; PMCID: PMC2756583

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Acetylation in the globular core of histone H3 on lysine-56 promotes chromatin disassembly during transcriptional activation

Jessica K. Tyler, PhD

Acetylation in the globular core of histone H3 on lysine-56 promotes chromatin disassembly during transcriptional activation

Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9000-5.

Williams SK, Truong D, Tyler JK.

PMID: 18577595; PMCID: PMC2449354

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Structural basis for the histone chaperone activity of Asf1

Jessica K. Tyler, PhD

Structural basis for the histone chaperone activity of Asf1

Cell. 2006 Nov 3;127(3):495-508.

English CM, Adkins MW, Carson JJ, Churchill ME, Tyler JK.

PMID: 17081973; PMCID: PMC2981792.

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Transcriptional activators are dispensable for transcription in the absence of Spt6-mediated chromatin reassembly of promoter regions

Jessica K. Tyler, PhD

Transcriptional activators are dispensable for transcription in the absence of Spt6-mediated chromatin reassembly of promoter regions

Mol Cell. 2006 Feb 3;21(3):405-16.

Adkins MW, Tyler JK.

Erratum in: Mol Cell. 2006 Apr 7;22(1):147-8.

PMID: 16455495

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The histone chaperone anti-silencing function 1 is a global regulator of transcription independent of passage through S phase

Jessica K. Tyler, PhD

The histone chaperone anti-silencing function 1 is a global regulator of transcription independent of passage through S phase

Mol Cell Biol. 2005 Jan;25(2):652-60.

Zabaronick SR, Tyler JK.

Erratum in: Mol Cell Biol. 2005 Apr;25(7):2871.

PMID: 15632066; PMCID: PMC543432

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Activation of the DNA damage checkpoint in yeast lacking the histone chaperone anti-silencing function 1

Jessica K. Tyler, PhD

Activation of the DNA damage checkpoint in yeast lacking the histone chaperone anti-silencing function 1

Mol Cell Biol. 2004 Dec;24(23):10313-27.  

Ramey CJ, Howar S, Adkins M, Linger J, Spicer J, Tyler JK.

PMID: 15542840; PMCID: PMC529054

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Chromatin disassembly mediated by the histone chaperone Asf1 is essential for transcriptional activation of the yeast PHO5 and PHO8 genes

Jessica K. Tyler, PhD

Chromatin disassembly mediated by the histone chaperone Asf1 is essential for transcriptional activation of the yeast PHO5 and PHO8 genes

Mol Cell. 2004 Jun 4;14(5):657-66.

Adkins MW, Howar SR, Tyler JK.

PMID: 15175160

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The RCAF complex mediates chromatin assembly during DNA replication and repair

Jessica K. Tyler, PhD

The RCAF complex mediates chromatin assembly during DNA replication and repair

Nature. 1999 Dec 2;402(6761):555-60.

Tyler JK, Adams CR, Chen SR, Kobayashi R, Kamakaka RT, Kadonaga JT.

PMID: 10591219

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The "dark side" of chromatin remodeling: repressive effects on transcription

Jessica K. Tyler, PhD

The "dark side" of chromatin remodeling: repressive effects on transcription

Cell. 1999 Nov 24;99(5):443-6.

Tyler JK, Kadonaga JT.

PMID: 10589670

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