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Michael D. Bulger, Ph.D.

Michael D. Bulger, Ph.D.

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About Me

Faculty Appointments

Associate Professor - Department of Pediatrics (SMD)

Associate Professor - Department of Biochemistry and Biophysics (SMD) - Joint

Credentials

Post-doctoral Training & Residency

Postdoctoral Fellowship, Fred Hutchinson Cancer Research Center, Seattle, WA. 1996 - 2003

Education

PhD | University of California at San Diego. Biology. 1996

BS | Pennsylvania State University. Molecular and Cell Biology. 1990

Awards

Beckman Young Investigators Award, Arnold and Mabel Beckman Foundation 2006

Burroughs Wellcome Fund Career Award in the Biomedical Sciences 2000

Excellence in Teaching Award, University of California, San Diego, CA 1992

Research

Dr. Bulger is interested in the interplay between tissue-specific gene expression and large-scale patterns of chromatin structure, as well as mechanisms by which enhancers and locus control regions (LCRs) mediate gene activation over large genomic distances. He addresses these questions using genes ...
Dr. Bulger is interested in the interplay between tissue-specific gene expression and large-scale patterns of chromatin structure, as well as mechanisms by which enhancers and locus control regions (LCRs) mediate gene activation over large genomic distances. He addresses these questions using genes up-regulated or specifically expressed during late erythroid differentiation, including the b-globin genes, as models. Ongoing or planned projects in his lab include:

(1) Modeling the formation of active chromatin domains in different experimental systems, including stably integrated transgenes in cell culture and reconstituted minichromosomes in cell-free extracts, in order to determine the cis-acting sequences and DNA-binding protein factors involved in their establishment and maintenance;

(2) Characterizing non-genic transcription within the b-globin locus, as well as other loci, and investigating the relationship between such transcription and domain-wide gene regulation;

(3) Identifying factors that facilitate enhancer-promoter and/or LCR-promoter communication at the b-globin locus, in order to gain clues as to how such communication occurs;

(4) Identifying factors that bind to 3'HS1 of the b-globin locus, which is the most prominent site of attachment to nuclear matrix at this region, in order to investigate the relationship between nuclear architecture and gene expression;

(5) Investigating the role of serine protease inhibitors (serpins) in chromatin condensation and gene regulation in differentiating erythroid cells.

Publications

Journal Articles

Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function

Fox S; Myers JA; Davidson C; Getman M; Kingsley PD; Frankiewicz N; Bulger M.

Nat Commun. 2020; : 4544.

Tucker C; Bhattacharya S; Wakabayashi H; Bellaousov S; Kravets A; Welle SL; Myers J; Hayes JJ; Bulger M; Rustchenko E.

Transcriptional Regulation on Aneuploid Chromosomes in Diverse

NuA4 histone acetyltransferase activity is required for H4 acetylation on a dosagecompensated

Environmentally-defined enhancer populations regulate diversity of tissue-resident macrophages.

Bulger M, Palis J

Trends in immunology.. 2015 February 36 (2):61-2. Epub 01/07/2015.

The chromatin "landscape" of a murine adult ?-globin gene is unaffected by deletion of either the gene promoter or a downstream enhancer.

Cadiz-Rivera B, Fromm G, de Vries C, Fields J, McGrath KE, Fiering S, Bulger M

PloS one.. 2014 9 (5):e92947. Epub 05/09/2014.

Maps for changing landscapes: viewing epigenomic signatures through differentiation.

Bulger M

Cell stem cell.. 2012 November 211 (5):581-2. Epub 1900 01 01.

Mitogen- and stress-activated kinase 1 (MSK1) regulates cigarette smoke-induced histone modifications on NF-?B-dependent genes.

Sundar IK, Chung S, Hwang JW, Lapek JD, Bulger M, Friedman AE, Yao H, Davie JR, Rahman I

PloS one.. 2012 7 (2):e31378. Epub 02/01/2012.

An embryonic stage-specific enhancer within the murine ?-globin locus mediates domain-wide histone hyperacetylation.

Fromm G, Cadiz-Rivera B, de Vries C, Getman M, McGrath KE, Kingsley PD, Fields J, Fiering S, Bulger M

Blood.. 2011 May 12117 (19):5207-14. Epub 02/14/2011.

A transient definitive erythroid lineage with unique regulation of the ?-globin locus in the mammalian embryo.

McGrath KE, Frame JM, Fromm GJ, Koniski AD, Kingsley PD, Little J, Bulger M, Palis J

Blood.. 2011 April 28117 (17):4600-8. Epub 03/04/2011.

Functional and mechanistic diversity of distal transcription enhancers.

Bulger M, Groudine M

Cell.. 2011 February 4144 (3):327-39. Epub 1900 01 01.

NF-?B inducing kinase, NIK mediates cigarette smoke/TNF?-induced histone acetylation and inflammation through differential activation of IKKs.

Chung S, Sundar IK, Hwang JW, Yull FE, Blackwell TS, Kinnula VL, Bulger M, Yao H, Rahman I

PloS one.. 2011 6 (8):e23488. Epub 08/24/2011.

Enhancers: the abundance and function of regulatory sequences beyond promoters.

Bulger M, Groudine M

Developmental biology.. 2010 March 15339 (2):250-7. Epub 12/16/2009.

Histone hyperacetylation within the beta-globin locus is context-dependent and precedes high-level gene expression.

Fromm G, de Vries C, Byron R, Fields J, Fiering S, Groudine M, Bender MA, Palis J, Bulger M

Blood.. 2009 October 15114 (16):3479-88. Epub 08/18/2009.

A spectrum of gene regulatory phenomena at mammalian beta-globin gene loci.

Fromm G, Bulger M

Biochemistry and cell biology = Biochimie et biologie cellulaire.. 2009 October 87 (5):781-90. Epub 1900 01 01.

RelB is differentially regulated by IkappaB Kinase-alpha in B cells and mouse lung by cigarette smoke.

Yang SR, Yao H, Rajendrasozhan S, Chung S, Edirisinghe I, Valvo S, Fromm G, McCabe MJ, Sime PJ, Phipps RP, Li JD, Bulger M, Rahman I

American journal of respiratory cell and molecular biology.. 2009 February 40 (2):147-58. Epub 08/07/2008.

IKK alpha causes chromatin modification on pro-inflammatory genes by cigarette smoke in mouse lung.

Yang SR, Valvo S, Yao H, Kode A, Rajendrasozhan S, Edirisinghe I, Caito S, Adenuga D, Henry R, Fromm G, Maggirwar S, Li JD, Bulger M, Rahman I

American journal of respiratory cell and molecular biology.. 2008 June 38 (6):689-98. Epub 01/31/2008.

Transcriptional interference among the murine beta-like globin genes.

Hu X, Eszterhas S, Pallazzi N, Bouhassira EE, Fields J, Tanabe O, Gerber SA, Bulger M, Engel JD, Groudine M, Fiering S

Blood.. 2007 March 1109 (5):2210-6. Epub 10/31/2006.

Flanking HS-62.5 and 3' HS1, and regions upstream of the LCR, are not required for beta-globin transcription.

Bender MA, Byron R, Ragoczy T, Telling A, Bulger M, Groudine M

Blood.. 2006 August 15108 (4):1395-401. Epub 04/27/2006.

"Maturational" globin switching in primary primitive erythroid cells.

Kingsley PD, Malik J, Emerson RL, Bushnell TP, McGrath KE, Bloedorn LA, Bulger M, Palis J

Blood.. 2006 February 15107 (4):1665-72. Epub 11/01/2005.

Deletion of the core region of 5' HS2 of the mouse beta-globin locus control region reveals a distinct effect in comparison with human beta-globin transgenes.

Hu X, Bulger M, Bender MA, Fields J, Groudine M, Fiering S

Blood.. 2006 January 15107 (2):821-6. Epub 09/27/2005.

Expression of adducin genes during erythropoiesis: a novel erythroid promoter for ADD2.

Yenerel MN, Sundell IB, Weese J, Bulger M, Gilligan DM

Experimental hematology.. 2005 July 33 (7):758-66. Epub 1900 01 01.

Hyperacetylated chromatin domains: lessons from heterochromatin.

Bulger M

The Journal of biological chemistry.. 2005 June 10280 (23):21689-92. Epub 04/19/2005.

A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse beta-globin locus.

Bulger M, Schübeler D, Bender MA, Hamilton J, Farrell CM, Hardison RC, Groudine M

Molecular and cellular biology.. 2003 August 23 (15):5234-44. Epub 1900 01 01.

Promoters of the murine embryonic beta-like globin genes Ey and betah1 do not compete for interaction with the beta-globin locus control region.

Hu X, Bulger M, Roach JN, Eszterhas SK, Olivier E, Bouhassira EE, Groudine MT, Fiering S

Proceedings of the National Academy of Sciences of the United States of America.. 2003 February 4100 (3):1111-5. Epub 01/13/2003.

TRAPping enhancer function.

Bulger M, Groudine M

Nature genetics.. 2002 December 32 (4):555-6. Epub 1900 01 01.

ChIPs of the beta-globin locus: unraveling gene regulation within an active domain.

Bulger M, Sawado T, Schübeler D, Groudine M

Current opinion in genetics & development.. 2002 April 12 (2):170-7. Epub 1900 01 01.

Interaction between the Drosophila CAF-1 and ASF1 chromatin assembly factors.

Tyler JK, Collins KA, Prasad-Sinha J, Amiott E, Bulger M, Harte PJ, Kobayashi R, Kadonaga JT

Molecular and cellular biology.. 2001 October 21 (19):6574-84. Epub 1900 01 01.

Multistep chromatin assembly on supercoiled plasmid DNA by nucleosome assembly protein-1 and ATP-utilizing chromatin assembly and remodeling factor.

Nakagawa T, Bulger M, Muramatsu M, Ito T

The Journal of biological chemistry.. 2001 July 20276 (29):27384-91. Epub 05/01/2001.

Comparative structural and functional analysis of the olfactory receptor genes flanking the human and mouse beta-globin gene clusters.

Bulger M, Bender MA, van Doorninck JH, Wertman B, Farrell CM, Felsenfeld G, Groudine M, Hardison R

Proceedings of the National Academy of Sciences of the United States of America.. 2000 December 1997 (26):14560-5. Epub 1900 01 01.

Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin locus in mice do not require the locus control region.

Bender MA, Bulger M, Close J, Groudine M

Molecular cell.. 2000 February 5 (2):387-93. Epub 1900 01 01.

Looping versus linking: toward a model for long-distance gene activation.

Bulger M, Groudine M

Genes & development.. 1999 October 113 (19):2465-77. Epub 1900 01 01.

Conservation of sequence and structure flanking the mouse and human beta-globin loci: the beta-globin genes are embedded within an array of odorant receptor genes.

Bulger M, van Doorninck JH, Saitoh N, Telling A, Farrell C, Bender MA, Felsenfeld G, Axel R, Groudine M, von Doorninck JH

Proceedings of the National Academy of Sciences of the United States of America.. 1999 April 2796 (9):5129-34. Epub 1900 01 01.

ACF, an ISWI-containing and ATP-utilizing chromatin assembly and remodeling factor.

Ito T, Bulger M, Pazin MJ, Kobayashi R, Kadonaga JT

Cell.. 1997 July 1190 (1):145-55. Epub 1900 01 01.

The p55 subunit of Drosophila chromatin assembly factor 1 is homologous to a histone deacetylase-associated protein.

Tyler JK, Bulger M, Kamakaka RT, Kobayashi R, Kadonaga JT

Molecular and cellular biology.. 1996 November 16 (11):6149-59. Epub 1900 01 01.

ATP-facilitated chromatin assembly with a nucleoplasmin-like protein from Drosophila melanogaster.

Ito T, Tyler JK, Bulger M, Kobayashi R, Kadonaga JT

The Journal of biological chemistry.. 1996 October 4271 (40):25041-8. Epub 1900 01 01.

Drosophila NAP-1 is a core histone chaperone that functions in ATP-facilitated assembly of regularly spaced nucleosomal arrays.

Ito T, Bulger M, Kobayashi R, Kadonaga JT

Molecular and cellular biology.. 1996 June 16 (6):3112-24. Epub 1900 01 01.

Postreplicative chromatin assembly by Drosophila and human chromatin assembly factor 1.

Kamakaka RT, Bulger M, Kaufman PD, Stillman B, Kadonaga JT

Molecular and cellular biology.. 1996 March 16 (3):810-7. Epub 1900 01 01.

Assembly of regularly spaced nucleosome arrays by Drosophila chromatin assembly factor 1 and a 56-kDa histone-binding protein.

Bulger M, Ito T, Kamakaka RT, Kadonaga JT

Proceedings of the National Academy of Sciences of the United States of America.. 1995 December 592 (25):11726-30. Epub 1900 01 01.

Biochemical reconstitution of chromatin with physiological nucleosome spacing

Bulger M, Kadonaga JT.

Methods Mol. Genet. 1994; 5: 241-262.

Potentiation of RNA polymerase II transcription by Gal4-VP16 during but not after DNA replication and chromatin assembly.

Kamakaka RT, Bulger M, Kadonaga JT

Genes & development.. 1993 September 7 (9):1779-95. Epub 1900 01 01.