Developmental and tissue expression patterns of histone macroH2A1 subtypes

Pehrson, John R.; Costanzi, Carl; Dharia, Chhaya

doi:10.1002/(sici)1097-4644(199704)65:1<107::aid-jcb11>3.0.co;2-h

Cited by 107 publications

(103 citation statements)

References 14 publications

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“…It has been suggested that macroH2A1.1 expression may be restricted to differentiated, non-proliferative tissues (Pehrson et al, 1997). To analyze any correlations between macroH2A1.1 protein expression and cell proliferation, we performed immunohistochemical stainings on tissue microarrays (TMAs) containing breast cancer samples of 260 patients (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Histone macroH2A isoforms predict the risk of lung cancer recurrence

Sporn¹,

Kustatscher²,

et al. 2009

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Section: Resultsmentioning

confidence: 99%

Histone macroH2A isoforms predict the risk of lung cancer recurrence

Sporn¹,

Kustatscher²,

et al. 2009

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“…We named these subtypes MACROH2A1.1 and MACROH2A1.2. The nucleotide sequences of cDNAs that encode MACROH2A1.1 and MACROH2A1.2 differed only in a single internal segment that encodes part of the nonhistone region (1,3), and these subtypes are formed by alternate splicing of a single gene, macroH2A1, on mouse chromosome 13 (4). Western blots of nuclear extracts from adult and fetal tissues revealed distinct tissue expression patterns that change during development (3).…”

mentioning

confidence: 99%

“…We identified two distinct MACROH2A cDNA sequences (1) and used specific antibodies to assign these sequences to the two MACROH2A proteins that were resolved by electrophoresis (3). We named these subtypes MACROH2A1.1 and MACROH2A1.2.…”

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confidence: 99%

MACROH2A2, a New Member of the MACROH2A Core Histone Family

Costanzi

Pehrson

2001

Journal of Biological Chemistry

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146

133

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MACROH2As are core histones that have a unique hybrid structure consisting of an amino-terminal domain that closely resembles a full-length histone H2A followed by a large nonhistone region. The human MACROH2A1 gene, on chromosome 5, encodes two MACROH2A subtypes, MACROH2A1.1 and MACROH-2A1.2, produced by alternate splicing. Here we report the identification of MACROH2A2, a new MACROH2A subtype encoded by a separate gene on human chromosome 10, MACROH2A2. The amino acid sequence of human MACROH2A2 is 68% identical to human MACROH2A1.2. We show by immunofluorescence on mouse tissue sections that MACROH2A2, like MACROH2A1.2, is concentrated in the inactive X chromosome. However, MACROH2A2 has a very different pattern of expression in the cell types present in the liver and kidney. When MACROH2A2 and MACROH2A1.2 are present in the same nucleus, they have a similar, though nonidentical, pattern of localization, with both subtypes present in the inactive X chromosome. Our results suggest a developmental role for MACROH2A subtypes.The MACROH2A core histones were first observed as two 42-kDa proteins that remained associated with rat liver mononucleosomes in 0.5 M NaCl (1). The sequences of cDNAs that encode these proteins revealed that they have a unique hybrid structure consisting of an amino-terminal domain that closely resembles a full-length histone H2A followed by a large nonhistone domain. MACROH2As are released from the nucleosome core at the same salt concentration as conventional H2As and appear to be released as a heterodimer with H2B (1). This indicates that the H2A region of MACROH2A replaces conventional H2A in the nucleosome core. It was estimated that 1 in 30 nucleosomes in rat liver would contain MACROH2A, assuming one MACROH2A per nucleosome (1). The H2A region (amino acids 1-122) is followed by a short linker region (10 amino acids) and then a region that is rich in basic amino acids (28 amino acids) (see Fig. 1). This basic region resembles basic tails present in other histones and most likely binds DNA.The nonhistone region of MACROH2As is a feature not found in other known core histones. It constitutes 57% of the protein and contains a putative leucine zipper motif consisting of four heptad repeats (1). The majority of the nonhistone region appears to have evolved from a gene of unknown function that originated prior to the appearance of eukaryotes (2). Among the sequences that are similar to the nonhistone region is a conserved domain present in proteins involved in the replication of RNA viruses (2).We identified two distinct MACROH2A cDNA sequences (1) and used specific antibodies to assign these sequences to the two MACROH2A proteins that were resolved by electrophoresis (3). We named these subtypes MACROH2A1.1 and MACROH2A1.2. The nucleotide sequences of cDNAs that encode MACROH2A1.1 and MACROH2A1.2 differed only in a single internal segment that encodes part of the nonhistone region (1, 3), and these subtypes are formed by alternate splicing of a single gene, macroH2A1, on mouse chromosome 1...

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“…Expression levels of macroH2A proteins correlate with the state of differentiation. 31,32 Loss of function approaches revealed a critical role for these histone variants in the differentiation but not the self-renewal of embryonic and adult stem cells. 34 Although macroH2As have well-characterized repressive functions, their influence on differentiation of embryonic stem cells is at least in part dependent on a pro-activating function of macroH2A1 on important differentiation regulatory genes such as Gata2 and Brachyury.…”

Section: Discussionmentioning

confidence: 99%

“…Plcγ1 is essential for erythropoietic differentiation TM Schnöder et al related gene product macroH2A1, are induced during various differentiation processes 31,32 and have been shown to contribute to the establishment and maintenance of the differentiated state. [33][34][35] Thus, we decided to investigate whether mH2A2 has a functional role in erythroid differentiation.…”

Section: Em (E) Quantitative Analysis (Paired T-test Two-tailed) Omentioning

confidence: 99%

Epo-induced erythroid maturation is dependent on Plcγ1 signaling

et al. 2014

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Erythropoiesis is a tightly regulated process. Development of red blood cells occurs through differentiation of hematopoietic stem cells (HSCs) into more committed progenitors and finally into erythrocytes. Binding of erythropoietin (Epo) to its receptor (EpoR) is required for erythropoiesis as it promotes survival and late maturation of erythroid progenitors. In vivo and in vitro studies have highlighted the requirement of EpoR signaling through Janus kinase 2 (Jak2) tyrosine kinase and Stat5a/b as a central pathway. Here, we demonstrate that phospholipase C gamma 1 (Plcγ1) is activated downstream of EpoR-Jak2 independently of Stat5. Plcγ1-deficient pro-erythroblasts and erythroid progenitors exhibited strong impairment in differentiation and colony-forming potential. In vivo, suppression of Plcγ1 in immunophenotypically defined HSCs (Lin − Sca1 + KIT + CD48 − CD150 + ) severely reduced erythroid development. To identify Plcγ1 effector molecules involved in regulation of erythroid differentiation, we assessed changes occurring at the global transcriptional and DNA methylation level after inactivation of Plcγ1. The top common downstream effector was H2afy2, which encodes for the histone variant macroH2A2 (mH2A2). Inactivation of mH2A2 expression recapitulated the effects of Plcγ1 depletion on erythroid maturation. Taken together, our findings identify Plcγ1 and its downstream target mH2A2, as a 'non-canonical' Epo signaling pathway essential for erythroid differentiation.

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Developmental and tissue expression patterns of histone macroH2A1 subtypes

Cited by 107 publications

References 14 publications

Histone macroH2A isoforms predict the risk of lung cancer recurrence

Histone macroH2A isoforms predict the risk of lung cancer recurrence

MACROH2A2, a New Member of the MACROH2A Core Histone Family

Epo-induced erythroid maturation is dependent on Plcγ1 signaling

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